Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial

Brown, Ryan M; Wang, Li; Coston, Taylor; Krishnan, Nathan I; Casey, Jonathan D; Wanderer, Jonathan P.; Ehrenfeld, Jesse M.; Byrne, Daniel W.; Stollings, Joanna L.; Siew, Edward D.; Bernard, Gordon R.; Self, Wesley H.; Rice, Todd W.; Semler, Matthew W.

doi:10.1164/rccm.201903-0557oc

Cited by 149 publications

(101 citation statements)

References 43 publications

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“…agree with the authors' assertions that balanced crystalloids are likely to be the most appropriate choice for critically ill patients experiencing sepsis, and respect the concerns about unequivocally recommending their judicious use (1). Although the critical care community awaits results from the PLUS (Plasma-Lyte 148 versus Saline) and BaSICS (Balanced Solution versus Saline in Intensive Care Study) studies, many institutions and providers are considering or already have implemented pathways and protocols for sepsis management that provide guidance for the choice of crystalloids during resuscitation.…”

supporting

confidence: 63%

“…When prior data are considered alongside the SMART post hoc analysis, the benefit on short-term mortality appears less certain, although potentially still impactful (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.76-1.01) (1, 3-5) (Figure 1). We have greater confidence in the decreased odds of patients developing acute kidney injury (OR, 0.67; 95% CI, 0.49-0.92) but uncertainty regarding progression to receipt of renal replacement therapy (OR, 0.85; 95% CI, 0.71-1.03) when receiving balanced crystalloids (1,(4)(5)(6). Although two of the three individual outcomes did not show significance, there was a lower incidence of major adverse kidney events in 30 days with balanced crystalloids compared with saline (OR, 0.78; 95% CI, 0.65-0.94) in the two studies that evaluated this outcome (1,6).…”

mentioning

confidence: 99%

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Balanced Crystalloids in Sepsis: Are We There Yet?

Hammond

Peksa

Rech

2020

Am J Respir Crit Care Med

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supporting

confidence: 63%

mentioning

confidence: 99%

Balanced Crystalloids in Sepsis: Are We There Yet?

Hammond

Peksa

Rech

2020

Am J Respir Crit Care Med

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“…In a post hoc analysis of septic patients (10.3% of patients) in this study, mean volume of fluid was higher compared with the overall population. Septic patients in the balanced crystalloids arm received 4458 ml compared with 4289 ml in the saline arm.…”

Section: Fluid Selection In Sepsismentioning

confidence: 55%

“…Although data are limited, pure stimulation of the α‐1 vasoreceptor with phenylephrine accelerates crystalloid distribution into the interstitial space, whereas mixed α‐1, β‐1 receptor stimulation by norepinephrine mitigates this process . Conversely, the pH‐lowering effects of saline may lead to higher doses of vasopressors for longer durations compared with balanced fluid resuscitation . Over‐resuscitation with fluids was also found to decrease the systemic vascular resistance, negating the intended therapeutic effect of the fluid or vasopressor used .…”

Section: Fluid Pharmacokinetics and Pharmacodynamics In The Septic Pamentioning

confidence: 99%

“…19 Conversely, the pH-lowering effects of saline may lead to higher doses of vasopressors for longer durations compared with balanced fluid resuscitation. 20 Over-resuscitation with fluids was also found to decrease the systemic vascular resistance, negating the intended therapeutic effect of the fluid or vasopressor used. 21 Hydrocortisone may also interact with the fluid compartments; pretreatment with this agent was shown to preserve glycocalyx integrity in both septic animal models and pilot surgical studies.…”

Section: Fluid Pharmacokinetics and Pharmacodynamics In The Septic Pamentioning

confidence: 99%

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Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta‐Analysis

2020

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This comprehensive review comparatively evaluates the safety and benefits of parenteral fluids used in resuscitation with a focus on sepsis. It also provides a random‐effects meta‐analysis of studies comparing restrictive resuscitation and usual care in sepsis with the primary outcome of mortality. In the septic patient, fluid therapy remains a complex interplay between fluid compartments in the body, the integrity of the endothelial barrier, and the inflammatory tone of the patient. Recent data have emerged describing the pharmacokinetics of fluid resuscitation that can be affected by the factors just listed, as well as mean arterial pressure, rate of infusion, volume of fluid infusate, nature of the fluid, and drug interactions. Fluid overload in sepsis has been associated with vasodilation, kidney injury, and increased mortality. Restrictive resuscitation after the initial septic insult is an emerging practice. Our search strategy of Medline databases revealed six randomized studies with 706 patients that examined restrictive resuscitation in sepsis. Results of this meta‐analysis demonstrated no differences in mortality with restrictive resuscitation compared with usual care (30.6% vs 37.8%; risk ratio 0.83, 95% confidence interval 0.66–1.05, respectively) but was limited by the small number of studies and larger quantities of pre‐randomization fluids. Another approach to address fluid overload is active (diuresis) de‐resuscitation strategies that may shorten the need for mechanical ventilation and intensive care unit length of stay. Data suggest that colloids may confer mortality benefit over saline in the most severely ill septic patients. Compared with isotonic saline, balanced resuscitation fluids are associated with a lower incidence of acute kidney injury and mortality. The benefits of balanced resuscitation fluids are most evident when higher volumes of fluids are used for sepsis. Clinicians should consider these pharmacotherapeutic factors when selecting a fluid, its quantity, and rate of infusion.

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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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Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial

Cited by 149 publications

References 43 publications

Balanced Crystalloids in Sepsis: Are We There Yet?

Balanced Crystalloids in Sepsis: Are We There Yet?

Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta‐Analysis

Fluid Therapy for Critically Ill Adults With Sepsis

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