Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults

Finfer, Simon; Micallef, Sharon; Hammond, Naomi; Navarra, Leanlove; Bellomo, Rinaldo; Billot, Laurent; Delaney, Anthony; Gallagher, Martin; Gattas, David; Li, Qiang; Mackle, Diane; Mysore, Jayanthi; Saxena, Manoj; Taylor, Colman; Young, Paul; Myburgh, John

doi:10.1056/nejmoa2114464

Cited by 189 publications

(150 citation statements)

References 31 publications

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“…Subsequently, we excluded 21 studies because of lack of appropriate outcome or population (included non-sepsis patients), secondary paper of included study, or conference abstracts of included or excluded studies. Eventually, 15 studies [ 11 , 12 , 13 , 14 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ] met our inclusion criteria and were included in the meta-analysis. Figure 1 shows the PRISMA flow chart that illustrates how the final studies were selected.…”

Section: Resultsmentioning

confidence: 99%

“…All the included studies were published between November 2013 and January 2022 and included patients with sepsis. Based on country of origin, six studies [ 24 , 27 , 28 , 29 , 30 , 33 ] originated from the USA, four studies [ 13 , 25 , 26 , 32 ] from Asia (China, India, Taiwan, and Thailand), two studies [ 14 , 23 ] from Europe (France and Italy), and two studies [ 11 , 31 ] from Australia and New Zealand, and one study [ 12 ] from Brazil. Regarding the design of studies, eight were RCTs [ 11 , 12 , 14 , 23 , 25 , 28 , 29 , 31 ] and seven [ 13 , 24 , 26 , 27 , 30 , 32 , 33 ] were retrospective cohort studies.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 20,329 patients with sepsis were included. Regarding enrollment location, ten studies [ 11 , 12 , 23 , 27 , 28 , 29 , 31 , 32 , 33 ] enrolled patients in ICU, four [ 14 , 24 , 25 , 26 ] in ED, and one [ 30 ] in both ED and ICU. A total of 9752 patients received BC, while 10,577 patients received NS.…”

Section: Resultsmentioning

confidence: 99%

“…All 15 studies [ 11 , 12 , 13 , 14 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], which included 20,329 patients with sepsis, reported overall mortality (21.1% in the BC group and 25.2% in the NS group). The overall mortality rate was lower in the BC group compared to NS group (RR 0.88, 95% CI 0.81–0.96, p = 0.005, I 2 = 51%, Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, in the SMART randomized controlled trial (RCT) in 2018 comparing NS to BC, the sepsis cohort was associated with lower 30-day mortality with BC compared to NS (odds ratio (OR) 0.90, 95% CI, 0.67, 0.94) [ 10 ]. However, more recent studies have been published comparing the effect of BC vs. NS on clinical outcomes in patients with sepsis and revealed conflicting findings [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

Beran

Altorok

Srour

et al. 2022

JCM

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The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81–0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79–0.95), and AKI (RR 0.85, 95% CI 0.77–0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90–1.03), need for RRT (RR 0.91, 95% CI 0.76–1.08), and ICU LOS (MD −0.25 days, 95% CI −3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82–1.02), AKI (RR 0.71, 95% CI 0.47–1.06), and need for RRT (RR 0.71, 95% CI 0.36–1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

Beran

Altorok

Srour

et al. 2022

JCM

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Fluid Therapy for Critically Ill Adults With Sepsis

Zampieri

Bagshaw

Semler

2023

JAMA

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ImportanceApproximately 20% to 30% of patients admitted to an intensive care unit have sepsis. While fluid therapy typically begins in the emergency department, intravenous fluids in the intensive care unit are an essential component of therapy for sepsis.ObservationsFor patients with sepsis, intravenous fluid can increase cardiac output and blood pressure, maintain or increase intravascular fluid volume, and deliver medications. Fluid therapy can be conceptualized as 4 overlapping phases from early illness through resolution of sepsis: resuscitation (rapid fluid administered to restore perfusion); optimization (the risks and benefits of additional fluids to treat shock and ensure organ perfusion are evaluated); stabilization (fluid therapy is used only when there is a signal of fluid responsiveness); and evacuation (excess fluid accumulated during treatment of critical illness is eliminated). Among 3723 patients with sepsis who received 1 to 2 L of fluid, 3 randomized clinical trials (RCTs) reported that goal-directed therapy administering fluid boluses to attain a central venous pressure of 8 to 12 mm Hg, vasopressors to attain a mean arterial blood pressure of 65 to 90 mm Hg, and red blood cell transfusions or inotropes to attain a central venous oxygen saturation of at least 70% did not decrease mortality compared with unstructured clinical care (24.9% vs 25.4%; P = .68). Among 1563 patients with sepsis and hypotension who received 1 L of fluid, an RCT reported that favoring vasopressor treatment did not improve mortality compared with further fluid administration (14.0% vs 14.9%; P = .61). Another RCT reported that among 1554 patients in the intensive care unit with septic shock treated with at least 1 L of fluid compared with more liberal fluid administration, restricting fluid administration in the absence of severe hypoperfusion did not reduce mortality (42.3% vs 42.1%; P = .96). An RCT of 1000 patients with acute respiratory distress during the evacuation phase reported that limiting fluid administration and administering diuretics improved the number of days alive without mechanical ventilation compared with fluid treatment to attain higher intracardiac pressure (14.6 vs 12.1 days; P &lt; .001), and it reported that hydroxyethyl starch significantly increased the incidence of kidney replacement therapy compared with saline (7.0% vs 5.8%; P = .04), Ringer lactate, or Ringer acetate.Conclusions and RelevanceFluids are an important component of treating patients who are critically ill with sepsis. Although optimal fluid management in patients with sepsis remains uncertain, clinicians should consider the risks and benefits of fluid administration in each phase of critical illness, avoid use of hydroxyethyl starch, and facilitate fluid removal for patients recovering from acute respiratory distress syndrome.

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Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis

Dulhunty,

Brett,

De Waele

et al. 2024

JAMA

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ImportanceWhether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain.ObjectiveTo evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis.Design, Setting, and ParticipantsAn international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis.InterventionEligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first.Main Outcomes and MeasuresThe primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality.ResultsAmong 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, −1.9% [95% CI, −4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different.Conclusions and RelevanceThe observed difference in 90-day mortality between continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients.Trial RegistrationClinicalTrials.gov Identifier: NCT03213990

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Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults

Cited by 189 publications

References 31 publications

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

Fluid Therapy for Critically Ill Adults With Sepsis

Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis

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