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65 Trial

65 Trial

JAMA

February 12, 2020

Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension.

Mazen Kherallah

Summarized by: 

What was the research question?

  • Does the reduction of exposure to vasopressors through permissive hypotension in older patients with vasodilatory shock, reduce 90-day mortality?


How did they do it?

  • A pragmatic, open, multicenter, parallel group, randomized clinical trial in 65 ICUs in the United Kingdom.

  • 2463 patients who were ≥65 years and had vasodilatory shock requiring vasopressors, were randomized to receive permissive hypotension with vasopressors to target MAP 60-65 mmHg (1221 patients) or standard care with a target MAP at the discretion of the ICU team (1242 patients).

  • Primary outcome was 90-day mortality.

  • Secondary outcomes included ICU and hospital mortality, duration of renal support, ICU and hospital length of stay, cognitive decline at 90 days and 1 year, and quality of life at 90 days and 1 year.


What did they find?

  • Mean age of 75 years and 57% were men.

  • Permissive hypotension group had a lower exposure to vasopressors compared to the standard group (median duration 33 hours vs 38 hours, and total dose in norepinephrine equivalents median, 17.7 mg vs 26.4 mg).

  • Mean MAP was 66.7 mmHg vs 72.6 mmHg.

  • 90-day mortality was not significantly better in permissive hypotension group compared to the standard group (41% vs. 43.8%, absolute risk difference, −2.85%; 95% CI, −6.75 to 1.05; P = .15).

  • Serious events were not different between the two groups: all adverse events (6.2% vs. 5.8%), acute renal failure (3.2% vs. 2.5%), and supraventricular cardiac arrhythmia (0.9% vs.1.0%).

  • Secondary endpoints were not significantly different between the two groups.

  • Subgroup analysis of patients with chronic hypertension revealed a lower 90-day mortality in the permissive hypotension group compared to the standard group (38.2% vs. 44.3%, OR 0.67, 95% CI, 0.49-0.85). No increase in rate of acute kidney injury was noticed in these patients.


Are there any limitations?

  • Unblinded study.

  • The study had a 90% power to detect a 6% absolute risk reduction.

  • The study was not powered for the Subgroup analysis.


What does it mean?

  • Permissive hypotension in patients with vasodilatory shock did not improve 90-day mortality compared to usual care.

  • No adverse events were reported with permissive hypotension.

  • It is safe to target MAP of 60-65 mmHg in elderly patients with vasodilatory shock.

  • Contrary to the SEPSISPAM trial, no increased rate of renal dysfunction in patients with chronic hypertension.

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