Evolving Management Practices for Early Sepsis-induced Hypoperfusion: A Narrative Review

Sepsis causes significant morbidity and mortality worldwide. Resuscitation is a cornerstone of management. This review covers five areas of evolving practice in the management of early sepsis-induced hypoperfusion: fluid resuscitation volume, timing of vasopressor initiation, resuscitation targets, route of vasopressor administration, and use of invasive blood pressure monitoring.

For each topic, we review the seminal evidence, discuss the evolution of practice over time, and highlight questions for additional research. Intravenous fluids are a core component of early sepsis resuscitation. However, with growing concerns about the harms of fluid, practice is evolving toward smaller-volume resuscitation, which is often paired with earlier vasopressor initiation. Large trials of fluid-restrictive, vasopressor-early strategies are providing more information about the safety and potential benefit of these approaches. Lowering blood pressure targets is a means to prevent fluid overload and reduce exposure to vasopressors; mean arterial pressure targets of 60–65 mm Hg appear to be safe, at least in older patients.

With the trend toward earlier vasopressor initiation, the need for central administration of vasopressors has been questioned, and peripheral vasopressor use is increasing, although it is not universally accepted. Similarly, although guidelines suggest the use of invasive blood pressure monitoring with arterial catheters in patients receiving vasopressors, blood pressure cuffs are less invasive and often sufficient. Overall, the management of early sepsis-induced hypoperfusion is evolving toward fluid-sparing and less-invasive strategies. However, many questions remain, and additional data are needed to further optimize our approach to resuscitation.

Target Audience

Pulmonologists, critical care specialists, translational researchers, and clinicians

Learning Objectives

At the conclusion of this activity, learners should be able to:

  • Describe new trial results on fluid restriction and early vasopressor initiation in sepsis-induced hypotension and identify gaps in current evidence
  • Use evidence-based approaches to monitor resuscitation in early sepsis
  • Apply noninvasive management strategies, including peripheral vasopressors and noninvasive blood pressure monitoring, in appropriate patients 
Course summary
Available credit: 
  • 1.00 AMA PRA Category 1 Credit(s)
    The American Thoracic Society designates this for a maximum of 1.00 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  • 1.00 Participation
Publication Date: 
Credit Expires: 

Accreditation Statement

The American Thoracic Society is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Disclosure Declaration

The current practice of the American Journal of Respiratory and Critical Care Medicine (AJRCCM) is to publish high quality, peer-reviewed and evidence-based original research, Concise Clinical Reviews, Guidelines and Consensus Statements. Articles published in AJRCCM include evidence-based summaries of optimal practice (Concise Clinical Reviews), evidence-based guidelines, workshop summaries and original contributions that will influence clinical practice. The publication of these articles by itself is only one piece of a multi-step process for the translation of evidence-based improvements in care to clinical practice. Articles selected for CME credit are designed to be the next step in the process of translating clinically relevant, evidence-based recommendations into clinical practice. This will be accomplished through a series of questions specifically designed by the author(s) to test that readers have the tools needed to translate recommendations for diagnostic and therapeutic clinical care into clinical practice. Members of the AJRCCM editorial board will review these questions and assess the quality of the questions based on:

  • Clarity,
  • Educational content, and
  • The quality of the evidence supporting the response to the question. Posttest questions will assess if practitioners have understood the most important recommendations available for the diagnosis and treatment of pulmonary diseases, critical illness, and sleep disorders and are able to implement them into clinical practice.

Article Authorship Disclosures (as submitted to the ATS prior to article publication date)

Elizabeth S. Munroe, M.D. (University of Michigan, Ann Arbor, MI, USA) reported receipt of a training grant, number T32 HL 007749 (Multidisciplinary Training Program in Lung Disease), from the National Institutes of Health. She received an honorarium for a talk related to peripheral vasopressor administration at Jefferson University (9/2022). She participates as a non-voting member of the DSMB for the VASSPR trial (Vasopressin for Septic Shock Pragmatic Trial), starting 1/2023.

Robert C. Hyzy, M.D. (University of Michigan, Ann Arbor, MI, USA) reported receipt of grant or contract NHLBI U-01 HL1230231 for the PETAL Network – CLOVERS clinical trial on sepsis patients.

Matthew W. Semler, M.D. (Vanderbilt University Medical Center, Nashville, TN, USA) received grant or contract K23HL143053 from the NHLBI. He served on an advisory board for Baxter International, Inc.

Manu Shankar-Hari, M.D., Ph.D. (The University of Edinburgh, Edinburgh, Scotland) reported no relevant financial relationships with ineligible companies.

Paul J. Young, M.B.Ch.B., Ph.D. (Monash University, Melbourne, Australia) received payments from Baxter Healthcare Pty for contribution to an intravenous fluid advisory board. He received payments from AM Pharma for acting as a member of the study management committee for a study investigating recombinant alkaline phosphatase in patients with septic acute kidney injury.

Fernando G. Zampieri, M.D., Ph.D. (University of Alberta, Edmonton, AB, Canada) received a grant for his institution from Ionis Pharmaceuticals. He has performed statistical consulting for Bactiguard in Sweden.

Hallie C. Prescott, M.D., M.Sc. (University of Michigan, Ann Arbor, MI, USA; VA Center for Clinical Management Research, Ann Arbor, MI, USA) reported that this material is the result of work supported with resources and use of facilities at the Ann Arbor VA Medical Center. Dr. Prescott reports grants from VA HSR&D, AHRQ, BC/BSM, and CDC, with money paid to her institution. Dr. Prescott reports payment from ISICEM to cover travel to the ISICEM conference in March 2022. Dr. Prescott participates on study DSMBs unrelated to this activity. Dr. Prescott is co-chair of the Surviving Sepsis Campaign Guidelines and physician-lead for a Michigan Statewide Sepsis quality collaborative sponsored by Blue Cross/Blue Shield of Michigan.

Disclosures of AJRCCM CME Planners

Dr. Schenck reported that he is a consultant for Axle Informatics

Off-Label Usage Disclosure



Edward Schenck, M.D.
Associate Editor, AJRCCM

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Available Credit

  • 1.00 AMA PRA Category 1 Credit(s)
    The American Thoracic Society designates this for a maximum of 1.00 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  • 1.00 Participation
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