SynthesisHealth technology assessment (Winchester, England)2021
Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT.
Synthesis in Health technology assessment (Winchester, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 4 syntheses or guidelines pooled it, 13 citations in OpenAlex.
- Health Economic Evaluations in Intensive Care: An Updated Systematic Review.Critical care explorations · 2025Pooled it
- Early management of adult sepsis and septic shock: Korean clinical practice guidelines.Acute and critical care · 2024Guideline
- The 2023 WSES guidelines on the management of trauma in elderly and frail patients.World journal of emergency surgery : WJES · 2024Guideline
- Hypotension during intensive care stay and mortality and morbidity: a systematic review and meta-analysis.Intensive care medicine · 2024Pooled it
- Rationale and design of a pilot randomized control trial of permissive hypotension after cardiac surgery: The PHACS trial.American heart journal plus : cardiology research and practice · 2026Article
- Mean arterial pressure at the initiation of continuous renal replacement therapy as a prognostic indicator in patients with acute kidney injury.Renal failure · 2025Observational
- Application of causal forests to randomised controlled trial data to identify heterogeneous treatment effects: a case study.BMC medical research methodology · 2025Article
- Permissive Hypotension in a Patient with Severe Hypernatremia: A Case Report.Clinical practice and cases in emergency medicine · 2024Article
- Norepinephrine May Exacerbate Septic Acute Kidney Injury: A Narrative Review.Journal of clinical medicine · 2023Review
- A Machine-Learning Approach for Estimating Subgroup- and Individual-Level Treatment Effects: An Illustration Using the 65 Trial.Medical decision making : an international journal of the Society for Medical Decision Making · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundVasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An individual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M,
objectiveTo estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60-65 mmHg) in older critically ill patients.
designA pragmatic, randomised clinical trial with integrated economic evaluation.
settingSixty-five NHS adult general critical care units.
participantsCritically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension.
interventionsIntervention - permissive hypotension (i.e. a mean arterial pressure target of 60-65 mmHg). Control (usual care) - a mean arterial pressure target at the treating clinician's discretion.
main outcome measuresThe primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year.
resultsOf 2600 patients randomised, 2463 (permissive hypotension, LIMITATIONS: The intervention was unblinded, with risk of bias minimised through central allocation concealment and a primary outcome not subject to observer bias. The control group event rate was higher than anticipated.
conclusionsIn critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension, permissive hypotension did not significantly reduce 90-day mortality compared with usual care. The absolute treatment effect on 90-day mortality, based on 95% confidence intervals, was between a 6.8-percentage reduction and a 1.1-percentage increase in mortality. FUTURE WORK: Future work should (1) update the individual patient data meta-analysis, (2) explore approaches for evaluating heterogeneity of treatment effect and (3) explore 65 trial conduct, including use of deferred consent, to inform future trials.
trial registrationCurrent Controlled Trials ISRCTN10580502.
fundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.