Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial

CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

Original languageEnglish
Pages (from-to)457-466
Number of pages10
JournalAnnals of Emergency Medicine
Volume72
Issue number4
DOIs
Publication statusPublished - 1 Oct 2018

Fingerprint

Fluid Therapy
Septic Shock
Resuscitation
Perfusion
National Heart, Lung, and Blood Institute (U.S.)
Acute Lung Injury
Secondary Prevention
Cardiac Output
Hypotension
Edema
Sepsis
Randomized Controlled Trials
Oxygen
Blood Pressure
Therapeutics

Cite this

CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators (2018). Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial. Annals of Emergency Medicine, 72(4), 457-466. https://doi.org/10.1016/j.annemergmed.2018.03.039
CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators. / Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock : Rationale for a Randomized Trial. In: Annals of Emergency Medicine. 2018 ; Vol. 72, No. 4. pp. 457-466.
@article{64eef978204a414c9453e1bdc72bcd72,
title = "Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial",
abstract = "Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.",
author = "{CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators} and Self, {Wesley H.} and Semler, {Matthew W.} and Rinaldo Bellomo and Brown, {Samuel M.} and deBoisblanc, {Bennett P.} and Exline, {Matthew C.} and Ginde, {Adit A.} and Grissom, {Colin K.} and Janz, {David R.} and Jones, {Alan E.} and Liu, {Kathleen D.} and Macdonald, {Stephen P.J.} and Miller, {Chadwick D.} and Park, {Pauline K.} and Reineck, {Lora A.} and Rice, {Todd W.} and Steingrub, {Jay S.} and Daniel Talmor and Yealy, {Donald M.} and Douglas, {Ivor S.} and Shapiro, {Nathan I.}",
year = "2018",
month = "10",
day = "1",
doi = "10.1016/j.annemergmed.2018.03.039",
language = "English",
volume = "72",
pages = "457--466",
journal = "Annals of Emergency Medicine",
issn = "0196-0644",
publisher = "Mosby International",
number = "4",

}

CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators 2018, 'Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial' Annals of Emergency Medicine, vol. 72, no. 4, pp. 457-466. https://doi.org/10.1016/j.annemergmed.2018.03.039

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock : Rationale for a Randomized Trial. / CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators.

In: Annals of Emergency Medicine, Vol. 72, No. 4, 01.10.2018, p. 457-466.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock

T2 - Rationale for a Randomized Trial

AU - CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators

AU - Self, Wesley H.

AU - Semler, Matthew W.

AU - Bellomo, Rinaldo

AU - Brown, Samuel M.

AU - deBoisblanc, Bennett P.

AU - Exline, Matthew C.

AU - Ginde, Adit A.

AU - Grissom, Colin K.

AU - Janz, David R.

AU - Jones, Alan E.

AU - Liu, Kathleen D.

AU - Macdonald, Stephen P.J.

AU - Miller, Chadwick D.

AU - Park, Pauline K.

AU - Reineck, Lora A.

AU - Rice, Todd W.

AU - Steingrub, Jay S.

AU - Talmor, Daniel

AU - Yealy, Donald M.

AU - Douglas, Ivor S.

AU - Shapiro, Nathan I.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

AB - Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

UR - http://www.scopus.com/inward/record.url?scp=85046641764&partnerID=8YFLogxK

U2 - 10.1016/j.annemergmed.2018.03.039

DO - 10.1016/j.annemergmed.2018.03.039

M3 - Article

VL - 72

SP - 457

EP - 466

JO - Annals of Emergency Medicine

JF - Annals of Emergency Medicine

SN - 0196-0644

IS - 4

ER -

CLOVERS Protocol Committee and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators. Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial. Annals of Emergency Medicine. 2018 Oct 1;72(4):457-466. https://doi.org/10.1016/j.annemergmed.2018.03.039