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Cited by 355Hemodynamic Monitoring and TherapySepsis Diagnosis and TreatmentHyperglycemia and glycemic control in critically ill and hospitalized patients

Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension: A Randomized Clinical Trial

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Lamontagne, François, Richards-Belle, Alvin, Thomas, Karen, Harrison, David A., Sadique, M. Zia, Grieve, Richard D., Camsooksai, Julie, Darnell, Robert +10 more·2020·JAMA
DOI 10.1001/jama.2020.0930PMC PMC7064880
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Abstract

Importance: Vasopressors are commonly administered to intensive care unit (ICU) patients to raise blood pressure. Balancing risks and benefits of vasopressors is a challenge, particularly in older patients. Objective: To determine whether reducing exposure to vasopressors through permissive hypotension (mean arterial pressure [MAP] target, 60-65 mm Hg) reduces mortality at 90 days in ICU patients aged 65 years or older with vasodilatory hypotension. Design, Setting, and Participants: A multicenter, pragmatic, randomized clinical trial was conducted in 65 ICUs in the United Kingdom and included 2600 randomized patients aged 65 years or older with vasodilatory hypotension (assessed by treating clinician). The study was conducted from July 2017 to March 2019, and follow-up was completed in August 2019. Interventions: Patients were randomized 1:1 to vasopressors guided either by MAP target (60-65 mm Hg, permissive hypotension) (n = 1291) or according to usual care (at the discretion of treating clinicians) (n = 1307). Main Outcome and Measures: The primary clinical outcome was all-cause mortality at 90 days. Results: Of 2600 randomized patients, after removal of those who declined or had withdrawn consent, 2463 (95%) were included in the analysis of the primary outcome (mean [SD] age 75 years [7 years]; 1387 [57%] men). Patients randomized to the permissive hypotension group had lower exposure to vasopressors compared with those in the usual care group (median duration 33 hours vs 38 hours; difference in medians, -5.0; 95% CI, -7.8 to -2.2 hours; total dose in norepinephrine equivalents median, 17.7 mg vs 26.4 mg; difference in medians, -8.7 mg; 95% CI, -12.8 to -4.6 mg). At 90 days, 500 of 1221 (41.0%) in the permissive hypotension compared with 544 of 1242 (43.8%) in the usual care group had died (absolute risk difference, -2.85%; 95% CI, -6.75 to 1.05; P = .15) (unadjusted relative risk, 0.93; 95% CI, 0.85-1.03). When adjusted for prespecified baseline variables, the odds ratio for 90-day mortality was 0.82 (95% CI, 0.68 to 0.98). Serious adverse events were reported for 79 patients (6.2%) in the permissive care group and 75 patients (5.8%) in the usual care group. The most common serious adverse events were acute renal failure (41 [3.2%] vs 33 [2.5%]) and supraventricular cardiac arrhythmia (12 [0.9%] vs 13 [1.0%]). Conclusions and Relevance: Among patients 65 years or older receiving vasopressors for vasodilatory hypotension, permissive hypotension compared with usual care did not result in a statistically significant reduction in mortality at 90 days. However, the confidence interval around the point estimate for the primary outcome should be considered when interpreting the clinical importance of the study. Trial Registration: isrctn.org Identifier: ISRCTN10580502.

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  • Ninety-day mortality in the permissive hypotension and usual care groups was similar (41.0% vs 43.8%).

    “Ninety-day mortality in the permissive hypotension and usual care groups was similar (41.0% vs 43.8%).”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [83]

  • Among 2463 analysed patients in that RCT, the permissive hypotension group had significantly less exposure to vasopressors, measured by duration of vasopressor infusion and total vasopressor doses in norepinephrine equivalents.

    “Among 2463 analysed patients, there was significantly less exposure to vasopressors in the intervention group, measured by duration of vasopressor infusion and total vasopressor doses expressed in norepinephrine equivalents.”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [83]

  • A recent RCT in patients aged 65 years and older with septic shock compared permissive hypotension (MAP 60-65 mm Hg) with usual care; the intervention group achieved a mean MAP of 66.7 mm Hg versus 72.6 mm Hg in usual care.

    “A recent RCT, monitored to ensure protocol and MAP target compliance, compared a “permissive hypotension” (MAP 60–65 mm Hg) group with a “usual care” group that received vasopressors and MAP targets set by the treating physician in patients aged 65 years and older with septic shock [82, 83]. The intervention group in this study achieved a mean MAP of 66.7 mm Hg, compared with 72.6 mm Hg in the”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [83]

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Authors
Lamontagne, F., Richards-Belle, A., Thomas, K., Harrison, D. A., Sadique, M. Z., Grieve, R. D., Camsooksai, J., Darnell, R., Gordon, A. C., Henry, D., Hudson, N., Mason, A. J., Saull, M., Whitman, C., Young, J. D., Rowan, K. M., Mouncey, P. R., & for the 65 trial investigators
Affiliations
  • Université de Sherbrooke (CA)
  • Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, United Kingdom
  • Intensive Care National Audit & Research Centre (GB)
  • London School of Hygiene and Tropical Medicine, Department of Health Services Research and Policy, London, United Kingdom
  • London School of Hygiene & Tropical Medicine (GB)
  • Poole Hospital NHS Foundation Trust (GB)
  • Imperial College Healthcare NHS Trust (GB)
  • Patient representative, United Kingdom
  • Kadoorie Centre for Critical Care Research and Education, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Corresponding author
Lamontagne, François
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2020-03-10
Volume
323
Issue
10
Pages
938
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2020.0930
PMC
PMC7064880
OpenAlex
W3005570206
Semantic Scholar
d44d7de805c5dae1f11d4adabaeaa349cb427428
Cited by
354
References
35
Citations by year
2026: 58 · 2025: 57 · 2024: 53 · 2023: 58 · 2022: 53 · 2021: 37 · 2020: 38
FWCI
42.50
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute for Health and Care Research (NIHR/CS/009/007, 15/80/39, RP-2015-06-018, HTA/15/80/39)
Topics
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords
vasopressors, permissive hypotension, older adults, critically ill patients, 90-day mortality, norepinephrine, mean arterial pressure targets, vasopressor dose reduction, intensive care unit, septic shock, fluid resuscitation
MeSH terms
Aged, Aged, 80 and over, Cognition Disorders, Female, Humans, Hypotension, Intensive Care Units, Male, Vasoconstrictor Agents, Confidence Intervals, Hospital Mortality, Atrial Premature Complexes, Kaplan-Meier Estimate, Acute Kidney Injury

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