Just a quick note looking at this lovely trial hypotension trial, evaluating potential use of lower mean arterial pressure targets in elderly patients receiving vasopressors.
Quick summary: Less is more. With a primary outcome of 90-day mortality, outcomes were no worse in patients randomized to a MAP target of 60-65 mmHg rather than “usual care” (≥65 mmHg) – 41.0% vs. 43.8% (-2.85%, 95%CI -6.75 to 1.05). Stated in formal terms, however, the trial failed to demonstrate a statistically significant difference between the treatment arms, and the confidence interval crosses unity. That said, I certainly agree with the accompanying editorial – it should be considered likely there is a potential advantage to “permitting” hypotension, rather than being hedging against intermittent dips. This trial wouldn’t go so far as to say the 65 mmHg is not the MAP target – patients in the “permissive” cohort still had a mean MAP on vasopressors of 66.7 mmHg, while those in the usual care arm trended higher at 72.6 mmHg – but, additional work looking at lower targets is reasonable.
There are, of course, minor oddities to be observed when considering how (or if) to generalize these data. While 78% of patients received norepinephrine, the second-most popular vasopressor was metaraminol, a predominately alpha agonist, used in almost a third of those randomized. Interestingly, fewer than half the patients enrolled were in “septic shock” by Sepsis-3 definitions, while only another quarter were noted to have “sepsis (not in shock)”. Finally, while the findings are generally consistent across all age cohorts, the mean age is ~75, and nearly 75% of those screened were excluded for one of many reasons.
This study is a lovely demonstration of a rather straightforward underlying principle – MAP is not a measure of tissue perfusion, and is used rather as a surrogate for the ultimately-important microvascular circulation. Making big tubes run at a higher pressure at the expense of clamping down little tubes may be harmful – hence the rationale for this trial, and future ones.
As another random aside, I might make a note here for aspiring researchers – the guidelines will frequently tell you where knowledge gaps exist. The 2012 Surviving Sepsis guidelines gave the MAP >65 target a “1C” recommendation, with “1” meaning consensus for the recommendation was strong, but “C” meaning the evidence was weak. Looking at guideline recommendations and their accompanying level of evidence provides: 1) clues as to which clinical questions are important enough to be addressed by guidelines, and 2) the gaps in the evidence. Guideline authors will even, frequently, explicitly call out certain clinical questions for further study. I wouldn’t go so far as to call it a roadmap to clarifying the important questions in your specialty, but it certainly could be fertile.
“Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension”
https://jamanetwork.com/journals/jama/fullarticle/2761427