65 Trial: Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension

Background

Low blood pressure is common in patients in intensive care. It is associated with a high risk of death. It can be treated with drugs called vasopressors. These drugs raise blood pressure, but also come with risks and side effects. Usually, a blood pressure target is used to guide how much of the drugs to give to patients.

Two previous clinical trials suggested that using a lower blood pressure target (and therefore giving less of the drugs) might reduce the number of deaths among older patients. However, although these results were promising, more research was needed to find out if they were correct.

Design

A total of 2600 patients aged ≥ 65 years who had low blood pressure in intensive care joined the trial. Half were randomly assigned to the new lower blood pressure target (less drugs). The other half were assigned to usual care (control group). As we had hoped, patients in the low blood pressure target group received less vasopressor drugs than the usual-care group.

Results

After 90 days, 41% of patients in the new low blood pressure target group had died, compared with 44% in the usual-care group. Although fewer patients died in the low blood pressure target group, the difference was small and may have occurred by chance. On average, the new target saved a small amount of money for the NHS.  

Conclusion

Although we could not prove that use of a lower blood pressure target saves lives for older patients in intensive care, our trial suggests that it might. Receiving less vasopressor drugs appeared safe for patients.

Who led the study?

  • Mr Paul Mouncey, ICNARC
  • Dr Francois Lamontagne, Université de Sherbrooke, Canada

This study is funded by the National Institute for Health Research (NIHR) – Health Technology Assessment (HTA) Programme (Project: 15/80/39)

Publications

Sadique Z, Grieve R, Diaz-Ordaz K, Mouncey P, Lamontagne F, O'Neill S. A Machine-Learning Approach for Estimating Subgroup- and Individual-Level Treatment Effects: An Illustration Using the 65 Trial. Med Decis Making 2022; 42(7):923-36. http://dx.doi.org/10.1177/0272989x221100717

Richards-Belle A, Hylands M, Muttalib F, Taran S, Rochwerg B, Day A, Mouncey PR, Radermacher P, Couban R, Asfar P, Adhikari NKJ, Lamontagne F. Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis. Crit Care Med 2023; 51(2):254-66. http://dx.doi.org/10.1097/ccm.0000000000005736

Mouncey PR, Richards-Belle A, Thomas K, Harrison DA, Sadique MZ, Grieve RD, Camsooksai J, Darnell R, Gordon AC, Henry D, Hudson N, Mason AJ, Saull M, Whitman C, Young JD, Lamontagne F, Rowan KM. Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT. Health Technol Assess 2021; 25(14):1-90. http://dx.doi.org/10.3310/hta25140

Thomas K, Patel A, Sadique MZ, Grieve RD, Mason AJ, Moler S, Gordon AC, Rowan KM, Mouncey PR, Lamontagne F, Harrison DA. Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension: Statistical and health economic analysis plan for the 65 trial in article. J Intensive Care Soc 2020; 21(3):230-1. http://dx.doi.org/10.1177/1751143720938894

Richards-Belle A, Mouncey PR, Grieve RD, Harrison DA, Sadique MZ, Henry D, Whitman C, Camsooksai J, Gordon AC, Young JD, Rowan KM, Lamontagne F. Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension: Protocol for the 65 randomised clinical trial. J Intensive Care Soc 2020; 21(4):281-2. http://dx.doi.org/10.1177/1751143720971433

Lamontagne F, Richards-Belle A, Thomas K, Harrison DA, Sadique MZ, Grieve RD, Camsooksai J, Darnell R, Gordon AC, Henry D, Hudson N, Mason AJ, Saull M, Whitman C, Young JD, Rowan KM, Mouncey PR, trial i. Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension: A Randomized Clinical Trial. JAMA 2020; :10.1001/jama.2020.0930. http://dx.doi.org/10.1001/jama.2020.0930