Restricted fluid failed to reduce mortality in sepsis-induced hypotension

A restrictive fluid strategy had no significant impact on mortality in patients with sepsis-induced hypotension compared to the typical liberal fluid strategy, based on data from 1,563 individuals.

Intravenous fluids are standard in the early resuscitation of sepsis patients, as are vasopressor agents, but data comparing restrictive or liberal use in these patients are limited, wrote Nathan I. Shapiro, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, and colleagues.

In a study published in the New England Journal of Medicine the researchers randomized 782 patients to the restrictive fluid group and 781 to the liberal fluid group. Patients aged 18 years and older were enrolled between March 7, 2018, and Jan. 31, 2022, at 60 centers in the United States. Participants were randomized within 4 hours of meeting the criteria for sepsis-induced hypotension that was refractory to initial treatment with 1-3 L of intravenous fluid. Baseline characteristics were similar between the groups. At randomization, 21% of patients in the restrictive fluid group and 18% in the liberal fluid group received vasopressors.

The primary outcome was 90-day all-cause mortality, which occurred in 109 and 116 patients in the liberal and restricted groups, respectively (approximately 14% of each group). No significant differences were noted among subgroups based on factors including systolic blood pressure and the use of vasopressors at randomization, chronic heart failure, end-stage renal disease, and pneumonia.

The restrictive fluid protocol called for vasopressors as the primary treatment for sepsis-induced hypotension, with “rescue fluids” to be used for prespecified situations of severe intravascular volume depletion. The liberal fluid protocol was a recommended initial intravenous infusion of 2,000 mL of isotonic crystalloid, followed by fluid boluses given based on clinical triggers such as tachycardia, along with “rescue vasopressors,” the researchers wrote.

The median volume of fluid administered in the first 24-hour period after randomization was 1,267 mL in the restrictive group and 3,400 mL in the liberal group. Adherence to the treatment protocols was greater than 90% for both groups.

The current study is distinct in its enrollment of patients with primary presentations of sepsis to a hospital emergency department, the researchers wrote in their discussion. “The patients who were enrolled in this trial were representative of the types of patients who present to the hospital with sepsis-induced hypotension; we expect our findings to be generalizable to these types of patients,” they said.

Reported serious adverse events were similar between the groups, though fewer episodes of fluid overload and pulmonary edema occurred in the restricted group.

The findings were limited by several factors including some cases in which patients in the restrictive group received more fluid than called for by the protocol, the researchers noted. Other limitations included the lack of subgroups with different coexisting conditions, the lack of blinding, and the lack of a control with no instructions for treatment protocol, they said. However, the results suggest that a restrictive fluid strategy had no significant advantage over a liberal strategy in terms of mortality for patients with sepsis-induced hypotension, they concluded.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shapiro disclosed serving as a consultant for and having stock options in Diagnostic Robotics, as well as grant support from Inflammatrix and Rapid Pathogen Screening, and serving as a consultant for Prenosis.

A restrictive fluid strategy had no significant impact on mortality in patients with sepsis-induced hypotension compared to the typical liberal fluid strategy, based on data from 1,563 individuals.

Intravenous fluids are standard in the early resuscitation of sepsis patients, as are vasopressor agents, but data comparing restrictive or liberal use in these patients are limited, wrote Nathan I. Shapiro, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, and colleagues.

In a study published in the New England Journal of Medicine the researchers randomized 782 patients to the restrictive fluid group and 781 to the liberal fluid group. Patients aged 18 years and older were enrolled between March 7, 2018, and Jan. 31, 2022, at 60 centers in the United States. Participants were randomized within 4 hours of meeting the criteria for sepsis-induced hypotension that was refractory to initial treatment with 1-3 L of intravenous fluid. Baseline characteristics were similar between the groups. At randomization, 21% of patients in the restrictive fluid group and 18% in the liberal fluid group received vasopressors.

The primary outcome was 90-day all-cause mortality, which occurred in 109 and 116 patients in the liberal and restricted groups, respectively (approximately 14% of each group). No significant differences were noted among subgroups based on factors including systolic blood pressure and the use of vasopressors at randomization, chronic heart failure, end-stage renal disease, and pneumonia.

The restrictive fluid protocol called for vasopressors as the primary treatment for sepsis-induced hypotension, with “rescue fluids” to be used for prespecified situations of severe intravascular volume depletion. The liberal fluid protocol was a recommended initial intravenous infusion of 2,000 mL of isotonic crystalloid, followed by fluid boluses given based on clinical triggers such as tachycardia, along with “rescue vasopressors,” the researchers wrote.

The median volume of fluid administered in the first 24-hour period after randomization was 1,267 mL in the restrictive group and 3,400 mL in the liberal group. Adherence to the treatment protocols was greater than 90% for both groups.

The current study is distinct in its enrollment of patients with primary presentations of sepsis to a hospital emergency department, the researchers wrote in their discussion. “The patients who were enrolled in this trial were representative of the types of patients who present to the hospital with sepsis-induced hypotension; we expect our findings to be generalizable to these types of patients,” they said.

Reported serious adverse events were similar between the groups, though fewer episodes of fluid overload and pulmonary edema occurred in the restricted group.

The findings were limited by several factors including some cases in which patients in the restrictive group received more fluid than called for by the protocol, the researchers noted. Other limitations included the lack of subgroups with different coexisting conditions, the lack of blinding, and the lack of a control with no instructions for treatment protocol, they said. However, the results suggest that a restrictive fluid strategy had no significant advantage over a liberal strategy in terms of mortality for patients with sepsis-induced hypotension, they concluded.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shapiro disclosed serving as a consultant for and having stock options in Diagnostic Robotics, as well as grant support from Inflammatrix and Rapid Pathogen Screening, and serving as a consultant for Prenosis.

A restrictive fluid strategy had no significant impact on mortality in patients with sepsis-induced hypotension compared to the typical liberal fluid strategy, based on data from 1,563 individuals.

Intravenous fluids are standard in the early resuscitation of sepsis patients, as are vasopressor agents, but data comparing restrictive or liberal use in these patients are limited, wrote Nathan I. Shapiro, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, and colleagues.

In a study published in the New England Journal of Medicine the researchers randomized 782 patients to the restrictive fluid group and 781 to the liberal fluid group. Patients aged 18 years and older were enrolled between March 7, 2018, and Jan. 31, 2022, at 60 centers in the United States. Participants were randomized within 4 hours of meeting the criteria for sepsis-induced hypotension that was refractory to initial treatment with 1-3 L of intravenous fluid. Baseline characteristics were similar between the groups. At randomization, 21% of patients in the restrictive fluid group and 18% in the liberal fluid group received vasopressors.

The primary outcome was 90-day all-cause mortality, which occurred in 109 and 116 patients in the liberal and restricted groups, respectively (approximately 14% of each group). No significant differences were noted among subgroups based on factors including systolic blood pressure and the use of vasopressors at randomization, chronic heart failure, end-stage renal disease, and pneumonia.

The restrictive fluid protocol called for vasopressors as the primary treatment for sepsis-induced hypotension, with “rescue fluids” to be used for prespecified situations of severe intravascular volume depletion. The liberal fluid protocol was a recommended initial intravenous infusion of 2,000 mL of isotonic crystalloid, followed by fluid boluses given based on clinical triggers such as tachycardia, along with “rescue vasopressors,” the researchers wrote.

The median volume of fluid administered in the first 24-hour period after randomization was 1,267 mL in the restrictive group and 3,400 mL in the liberal group. Adherence to the treatment protocols was greater than 90% for both groups.

The current study is distinct in its enrollment of patients with primary presentations of sepsis to a hospital emergency department, the researchers wrote in their discussion. “The patients who were enrolled in this trial were representative of the types of patients who present to the hospital with sepsis-induced hypotension; we expect our findings to be generalizable to these types of patients,” they said.

Reported serious adverse events were similar between the groups, though fewer episodes of fluid overload and pulmonary edema occurred in the restricted group.

The findings were limited by several factors including some cases in which patients in the restrictive group received more fluid than called for by the protocol, the researchers noted. Other limitations included the lack of subgroups with different coexisting conditions, the lack of blinding, and the lack of a control with no instructions for treatment protocol, they said. However, the results suggest that a restrictive fluid strategy had no significant advantage over a liberal strategy in terms of mortality for patients with sepsis-induced hypotension, they concluded.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shapiro disclosed serving as a consultant for and having stock options in Diagnostic Robotics, as well as grant support from Inflammatrix and Rapid Pathogen Screening, and serving as a consultant for Prenosis.