Prospective Trial of Alerting to Extended Hypotensive Exposures on Long-Term Outcome After Surgery

Background:

We recently identified a significant association of postoperative morbidity and 30-day
mortality with the concept of "hypotensive exposures" during anaesthesia. Specifically, we
found in approximately 160,000 patients from 3 institutions (Cleveland Clinic, Vanderbilt
University and Saint Louis University) that roughly every third adult patient undergoing a
non-cardiac procedure under anaesthesia experienced twice the 30-day all-cause mortality
portended by extended cumulative periods of less than normal intraoperative blood pressure.
This association was independent of co-morbidity (Charlson Co-morbidity index), causing the
same relative increase in mortality in "healthy" as in "sick" patients. A new method was
introduced to quantify hypotensive exposures in form of a novel risk score called the
SLUScore™, a score with values from ranging from 0 (no hypotensive exposure) to a maximum of
31 (the maximal number of exposures exceeded of a certain risk-based set of limits for time
accumulated at a mean arterial blood pressure below thresholds between 75 and 45 mm Hg), with
each increment of the SLUScore™ portending an equivalent 5% increase in 30-day postoperative
mortality.

Hypothesis:

We test the hypothesis that alerting the anaesthesia care team to progressive hypotensive
exposures (a progressive increase in their SLUScore™) improves 30-day survival. This will be
tested in a prospective, randomised trial.

Methods and Design:

A novel Clinical Decision Support System (ACG-Anesthesia by Talis Clinical, LLC) will be used
to alert anaesthesia care team members to patients' SLUScores™ in near real time (within 1
minute of documented exposures). At the time of transition from a SLUScore™ of 0 to 1
(occurring in approximately every third anaesthetic), patients will be automatically
randomized by the ACG-Anesthesia system to either alert or no alert (blinded) status with the
intent of raising awareness on the part of the anaesthesia care team in the alert group of
the occurrence of extended hypotensive exposures and their associated risk, allowing the team
to render its best clinical judgment to initiate interventions aimed at bringing patients out
of progressive hypotensive states. With one interim analysis planned after two years, a total
of 56,248 patients are projected to be enrolled over a 4-year period for this trial to be
powered to detect a 0.3% absolute reduction in 30-day mortality, by saving at least 50 lives
in the alert group after two years (two-sided p<0.016) or at least 70 lives (two-sided
p<0.019) at the conclusion of the trial.

Inclusion Criteria:

- Any adult patient presenting for any type of non-cardiac procedure performed under any
type of anesthesia

Exclusion Criteria:

- Pediatric patients (< 18 yrs of age)

- Obstetric patients