Triple-low Alerts Do Not Reduce Mortality: A Real-time Randomized Trial

Triple-low events (mean arterial pressure less than 75 mmHg, Bispectral Index less than 45, and minimum alveolar fraction less than 0.8) are associated with mortality but may not be causal. This study tested the hypothesis that providing triple-low alerts to clinicians reduces 90-day mortality.

Adults having noncardiac surgery with volatile anesthesia and Bispectral Index monitoring were electronically screened for triple-low events. Patients having triple-low events were randomized in real time, with clinicians either receiving an alert, "consider hemodynamic support," or not. Patients were blinded to treatment. Helpful responses to triple-low events were defined by administration of a vasopressor within 5 min or a 20% reduction in end-tidal volatile anesthetic concentration within 15 min.

Of the qualifying patients, 7,569 of 36,670 (20%) had triple-low events and were randomized. All 7,569 were included in the primary analysis. Ninety-day mortality was 8.3% in the alert group and 7.3% in the nonalert group. The hazard ratio (95% CI) for alert versus nonalert was 1.14 (0.96, 1.35); P = 0.12, crossing a prespecified futility boundary. Clinical responses were helpful in about half the patients in each group, with 51% of alert patients and 47% of nonalert patients receiving vasopressors or having anesthetics lowered after start of triple low (P < 0.001). There was no relationship between the response to triple-low events and adjusted 90-day mortality.

Real-time alerts to triple-low events did not lead to a reduction in 90-day mortality, and there were fewer responses to alerts than expected. However, similar mortality with and without responses suggests that there is no strong relationship between responses to triple-low events and mortality.