Triple-Low Alerts Do Not Reduce 90-Day Mortality

Author: Michael Vlessides

Anesthesiology News

A large study from the Cleveland Clinic has concluded that real-time alerts to triple-low events do not reduce 90-day mortality in adults undergoing noncardiac surgery with volatile general anesthesia. The alerts involved mean arterial pressure less than 75 mm Hg, bispectral index below 45, and minimum alveolar concentration less than 0.8.

Although the trial also found fewer clinician responses to alerts than expected, the similar mortality rates with and without clinician responses suggest that a strong relationship between responses to triple-low events and death does not exist.

“Several previous studies showed that triple-low events predict postoperative mortality,” said Daniel I. Sessler, MD, the Michael Cudahy Professor and Chair of the Department of Outcomes Research at Cleveland Clinic in Ohio. “No one component—low MAP, low BIS or low MAC—was especially predictive. But any two of them combined roughly doubled mortality, and the three combined quadrupled mortality [Anesthesiology 2012;116(6):1195-1203].

“The question, of course, was whether this is a causal relationship or whether it simply predicted deaths that we couldn’t prevent,” Dr. Sessler said. “We therefore tested the primary hypothesis that alerting clinicians to triple-low events reduces 90-day postoperative mortality.”

“The study design was innovative in that randomization was on the fly,” Dr. Sessler explained. “With [institutional review board] approval and waived consent, qualifying patients were randomized in real time. The allocations were to generate an alert for clinicians or not.”

Alerts appeared on the electronic health record screen as “A triple-low (MAP, MAC, and BIS) condition has been detected. Consider hemodynamic support.” At the same time, a page was sent to both the in-room clinician and the attending anesthesiologist.

“Clinicians were free to act on the alert if they deemed it appropriate, but they were not required to respond in any particular way,” Dr. Sessler said.

Helpful responses by clinicians to triple-low events were characterized by the administration of a vasopressor within five minutes of the alert or a 20% reduction in end-tidal volatile anesthetic concentration within 15 minutes. Patients were blinded to treatment.

“It’s obvious from our enrollment numbers that the study would have been impossible as a conventional randomized trial because we would have had to consent more than 35,000 patients,” Dr. Sessler said. “But using this novel real-time randomization approach, the trial became practical.”

As Dr. Sessler reported at the 2018 annual meeting of the American Society of Anesthesiologists, 90-day mortality was 8.3% in the alert group (313/3,674) and 7.3% in the non-alert group (279/3,805).

The hazard ratio (HR) for alert versus non-alert was 1.14 (95% CI, 0.96-1.35; P= 0.12). Similarly, nonsignificant hazard ratios were found between groups for both 30-day mortality (HR, 1.10; 95% CI, 0.89-1.66; P=0.36) and one-year mortality (HR, 0.98; 95% CI, 0.87-110; P=0.71).

Interestingly, the study also revealed that clinicians’ responses were similar among patients who did and did not receive triple-low alerts. Indeed, 51% of alert patients and 47% of non-alert patients either received vasopressors or had their anesthetics lowered after the start of the triple-low event.

“It is clear that clinicians didn’t take the study seriously,” Dr. Sessler said. “They simply didn’t respond very effectively to the alerts.”

Most telling was a finding that no significant relationship was seen between the response to triple-low alerts and adjusted 90-day mortality (Table).

“We therefore conclude, based on previous work, that triple-low events predict mortality and, based on current results, that neither alerts nor interventions for triple-low events reduce 90-day or 30-day mortality,” Dr. Sessler said. “A corollary is that triple-low events are not causally related to mortality.”

Dr. Sessler cautioned that although the current study confirms that a MAP of 75 mm Hg or higher is safe for most patients, “pressures less than 65 mm Hg are associated with myocardial injury, acute kidney injury and death. Furthermore, postoperative hypotension is common, profound and prolonged—and the postoperative period is where much patient injury occurs.”

Alerts Often Ignored

As Miklos D. Kertai, MD, PhD, discussed, getting physicians to change practice can be a challenge unto itself. “I think there are two different messages in their publication,” said Dr. Kertai, a professor of anesthesiology at Vanderbilt University Medical Center, in Nashville, Tenn. “One is that they were unable to provide substantial evidence that intervening on triple-low alerts could improve the outcomes of these patients.

“The lack of evidence that intervening on triple-low alerts could improve outcomes reinforces our previous findings [Anesthesiology 2014;121(1):18-28], which show that patient- or procedure-related characteristics play a substantial role in the risk of postoperative outcomes, not anesthetic management.

“But a potentially more important message is that these alerts were often ignored or not taken into consideration,” Dr. Kertai said, “and that may have influenced their outcomes too.”