The DOI matches its Crossref record, with a small difference in title or year; 29 of the 29 references it cites were found in a registry or an index.
Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN 20769191.
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In the citing paper
“Most studies were observational, and there are concerns that de-escalation is used primarily in patients who are getting better, which is why the reported improved short-term mortality should be interpreted with caution (277,279).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [279]
Experimental — accuracy not yet measuredIn the citing paper
“Although there was no difference with respect to kidney injury (RR 0.89; 95% CI 0.72–1.11), vasopressin use reduced the risk of RRT (RR 0.71; 95% CI 0.53–0.97) [354].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [354]
In the citing paper
“There was no significant difference between the vasopressin and norepinephrine groups in 28-day mortality [30.9% vs 27.5%; RR 1.13 (95% CI 0.85–1.51).”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [354]
In the citing paper
“Several meta-analyses suggest decreased mortality in patients with a pressure- and volume-limited strategy for established ARDS [353, 354].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [354]
In the citing paper
“In the ADRENAL [479] study, hydrocortisone was administered for a maximum of seven days or until ICU discharge or death; in APROCCHSS [478] hydrocortisone was administered for seven days; in VANISH [354] 200 mg of hydrocortisone was administered daily for 5 days and then tapered over further 6 days.”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [354]
In the citing paper
“Since then, three large RCTs have been published [354, 478, 479].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [354]
In the citing paper
“The optimal dose, timing of initiation, and duration of corticosteroids remain uncertain; recent RCTs used 200 mg per day of IV hydrocortisone in divided doses [354, 479].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [354]
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Metadata
- Authors
- Gordon, A. C., Mason, A. J., Thirunavukkarasu, N., Perkins, G. D., Cecconi, M., Cepkova, M., Pogson, D. G., Aya, H. D., Anjum, A., Frazier, G. J., Santhakumaran, S., Ashby, D., Brett, S. J., & for the VANISH Investigators
- Affiliations
- Imperial College London (GB)
- London School of Hygiene & Tropical Medicine (GB)
- University of Warwick (GB)
- National Health Service (GB)
- Corresponding author
- Gordon, Anthony C.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2016-08-02
- Volume
- 316
- Issue
- 5
- Pages
- 509
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2489536306
- Semantic Scholar
- 0a2e8f0595aed35457448e71c5f52e2cd0ccb618
- Cited by
- 728
- References
- 29
- Citations by year
- 2026: 77 · 2025: 114 · 2024: 82 · 2023: 69 · 2022: 59 · 2021: 61 · 2020: 67 · 2019: 83 · 2018: 62 · 2017: 40 · 2016: 12
- FWCI
- 61.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- University of Brighton Repository (University of Brighton) (publishedVersion, other-oa)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Warwick Research Archive Portal (University of Warwick) (submittedVersion)
- Funders
- University of Portsmouth
- Intensive Care Foundation
- University Hospital Southampton NHS Foundation Trust
- National Institute for Health and Care Research (NF-SI-0514-10139, NIHR/CS/009/007, PB-PG-0610-22350)
- Imperial College London
- Imperial College Healthcare NHS Trust
- Barts Health NHS Trust
- University Hospitals Coventry and Warwickshire NHS Trust
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Keywords
- septic shock, vasopressin, norepinephrine, renal failure, acute kidney injury, vasopressor therapy, cortisol, renal replacement therapy, mortality, intensive care unit patients, fluid resuscitation, serious adverse events, 90-day outcomes
- MeSH terms
- Adult, Aged, Aged, 80 and over, Critical Care, Double-Blind Method, Drug Administration Schedule, Female, Fluid Therapy, United Kingdom, Humans, Hydrocortisone, Intensive Care Units, Male, Middle Aged, Norepinephrine, Shock, Septic, Vasoconstrictor Agents, Vasopressins, Treatment Outcome, Renal Replacement Therapy, Renal Insufficiency
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