Finding the Optimal Fluid Strategy for Sepsis

The new review offers an evidence-based strategy for improving sepsis outcomes with appropriate doses of intravenous (IV) fluid therapy at each stage of treatment.

The document offers guidance on four forms of liquid use; assess whether administration of IV fluids is indicated; and purpose of fluid therapy, timing, type, and other clinical parameters. The recommendations were based on a literature search that included 28 randomized clinical trials (RCTs), seven secondary analyzes of RCTs, 20 observational studies, five systematic reviews or meta-analyses, one scoping review, one practice guideline, and 14 references of references. review.

Dr. Fernando Zampieri

“Our review highlights that crystalloids should remain the standard of care for the majority of critically ill patients, especially during early resuscitation,” Fernando G. Zampieri, MD, PhD, assistant professor of critical care medicine at the University of Alberta and Alberta Health Services in Edmonton , Alberta, Canada, told Medscape Medical News. “In particular, starch should not be used in critically ill patients. A balanced solution may be preferable for most patients, except for patients with traumatic brain injury, in which a 0.9% saline solution is recommended.”

The review was published online June 13 in Journal of the American Medical Association.

Four Phases of Therapy

Approximately 20%-30% of patients admitted to intensive care units have sepsis, and fluid therapy is a key component of their care. Although IV fluids can increase cardiac output and blood pressure, maintain or increase intravascular fluid volume, and administer medications, too much fluid or the wrong type of fluid can be harmful.

“Deciding which type of fluid is best for the patient [with sepsis] can be challenging,” Zampieri said.

Fluid therapy can be conceptualized as spanning four overlapping phases from initial illness to resolution of sepsis, according to the review. These phases include resuscitation (quick administration of fluids to restore perfusion), optimization (assessing the risks and benefits of additional fluids to treat shock and ensure organ perfusion), stabilization (using fluid therapy only if there is a signal of a fluid response), and evacuation (removing fluid therapy). excess fluid accumulated during treatment).

The review describes studies that support its key recommendations for management in this phase. Three RCTs included 3723 patients with sepsis who received 1-2 L of fluids. They found that treatment was goal-directed with fluid boluses to achieve a central venous pressure of 8–12 mm Hg, vasopressors to achieve a mean arterial blood pressure of 65–90 mm Hg, and red cell transfusion or inotropes to achieve venous oxygen saturation. at least 70% did not reduce mortality, compared with unstructured clinical care (24.9% vs 25.4%, P = 0.68).

One RCT with 1563 patients with sepsis and hypotension who received 1 L of fluids found that vasopressor treatment did not increase mortality, compared with further fluids (14.0% vs. 14.9%, P = 0.61).

In another RCT, among 1554 patients with septic shock admitted to the intensive care unit with at least 1 L of fluids, fluid restriction in the absence of severe hypoperfusion did not reduce mortality, compared with more liberal administration of fluids (42.3% vs. 42 ,1%, P = 0.96).

An RCT of 1000 patients with acute respiratory distress during the evacuation phase found that fluid restriction and administration of diuretics increased the number of days alive without mechanical ventilation, compared with fluid maintenance to achieve higher intracardiac pressure (14.6 vs 12.1 days, P < 0.001).

This study also found that hydroxyethyl starch significantly increased the incidence of renal replacement therapy, compared with saline (7.0% vs. 5.8%, P = 0.04), Ringer’s lactate, or Ringer’s acetate.

Ultrasound Lacks Validation

The authors summarize the main concerns regarding fluid therapy. Fluid therapy should be initiated for patients with evidence of sepsis-induced hypoperfusion who are likely to increase cardiac output with fluid administration, they wrote. Fluid administration should be discontinued when evidence of hypoperfusion resolves, the patient is no longer responding to fluids, or the patient shows evidence of fluid overload.

Balanced solutions should be chosen over 0.9% saline for fluid therapy, according to reviews. Hydroxyethyl starch should not be used.

Fluid elimination should be considered after the resuscitation and optimization phase and when the patient has stabilized, the authors write. Diuretics are the first-line therapy to facilitate fluid elimination.

Renal replacement therapy may be considered for patients with severe acute kidney injury who are complicated by fluid overload and are unresponsive to diuretic therapy.

“The use of ultrasound as a bedside tool to guide fluid resuscitation holds promise but lacks validation in robust randomized controlled trials,” said Zampieri. “Point-of-care ultrasound may be useful to assess the cause of shock and [helping to exclude] life-threatening diagnosis at presentation, such as cardiac tamponade.”

Pending the emergence of further evidence, the authors suggest that clinicians prescribe fluids judiciously, preferably by aliquots followed by frequent reassessments. “Setting resuscitation targets (such as capillary refill time or lactate, among others) and performing a fluid challenge to correct them while no signs of fluid overload (such as pulmonary edema) are occurring is a common practice that is also supported by clinical research,” says Zampieri.

He added that the review’s recommendations were based on research conducted primarily in high-income neighborhoods, and that generalizability would depend on factors such as local standards of care and availability of resources.

“Our review provides overall guidance, but caution is needed before extrapolating the suggestions to every possible clinical scenario,” he concluded.

Liquids as Drugs

Comment on reviews for Medscape, Hernando Gomez, MD, MPH, a professor of critical care medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, said, “I agree with the conclusions and commend the authors for this highly practical literature revision.” Gomez was not involved in the review.

Dr. Hernando Gómez

“I want to emphasize that although fluids can be dangerous, especially when they are not indicated and when overused, fluid resuscitation in a septic patient who has evidence of hypoperfusion is paramount,” he said.

“The relationship between fluid accumulation and poor outcome is truly a Goldilocks problem, often described in the literature as a ‘U’ shape, in which there is too little fluid (i.e., a very restrictive strategy) or too much fluid (i.e., overuse and not according to the patient’s needs) can be dangerous,” said Gomez.

Furthermore, any strategy for assessing fluid responsiveness has limitations. “It’s key that clinicians resist the temptation to ignore these limitations, because decisions made based on flawed data are just as dangerous as not assessing fluid response in the first place,” he said.

Based on the evidence, clinicians should think of fluids as medicine and carefully assess the risks and benefits before deciding to give fluids to their patients, added Gomez. It is also important to separate the question “Does my patient need fluids?” from the question “Is my patient responsive to fluids?”

“These are two different questions that often get mixed up,” Gomez said. “If a fluid bolus is given to a patient who needs fluids and responsiveness to fluid does not improve tissue perfusion, then fluids should not be given.”

No funds have been reported for the review. Zampieri reported receiving fluids and logistics from Baxter Hospitalar during the implementation of the BaSICS trial, personal expenses from Bactiguard for statistical consultations and from Baxter for participation on the advisory board, grants from Ionis Pharmaceuticals outside of the work assigned, and serving as principal investigator of the BaSICS trial . Gomez reports no relevant financial relationships.

JAMA. Published online 13 June 2023. Abstract.

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