Triple-low Alerts Do Not Reduce Mortality

Abstract

EDITOR’S PERSPECTIVE What We Already Know about This Topic Intraoperative triple-low events (mean arterial pressure less than 75 mmHg, Bispectral Index less than 45, and minimum alveolar fraction of anesthetic less than 0.8) have been found to be associated with increased risk of mortality What This Article Tells Us That Is New A randomized electronic alert of triple-low events to treating clinicians did not reduce 90-day mortality The alerts minimally influenced clinician responses, assessed as vasopressor administration or reduction in end-tidal volatile anesthetic partial pressure, and there was no association between response to alerts and mortality Triple-low events predict mortality but do not appear to be causally related Background 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. Methods 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. Results 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. Conclusions 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.

Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk Noncardiac Surgery

“…For example, a randomized trial of alerts for Triple Low episodes (low Bispectral Index, low systolic pressure, and low anesthetic concentration) failed because clinicians largely ignored the warnings. 18 Clear treatment guidance and education focused on compliance should be integral to future trials using index guidance. In summary, the index predicted hypotension, but the use of index failed to reduce hypotension.…”

Novel Clinical Trial Designs to Improve the Efficiency of Research

“…The primary outcome was 90-day mortality. 40 Both trials were considered ethical, and consent was waived by the Cleveland Clinic (Cleveland, Ohio) institutional review board because alerts were unlikely to have been harmful, were possibly helpful, and because the trial would be impractical without waived consent. In both cases, the alerts proved to be unhelpful but also harmless.…”

Induced pluripotent stem cells as a platform to understand patient‐specific responses to opioids and anaesthetics

“…• Individual responses to anaesthetics and pain medications may depend on genetic differences. For instance, while the number and type of Na + channels expressed within the dorsal ganglion may explain the diverse response to analgesics in chronic pain patients (Chang et al, 2018;Meents et al, 2019), other patients suffer from a condition labelled as "triple low" (i.e., patients presenting with low BP and low cerebral electrical activity despite being exposed to a low concentration of anaesthetics) that increases perioperative morbidity and mortality (Sessler et al, 2012(Sessler et al, , 2019. These associations suggest a strong link between pharmacogenetics and perioperative cardiovascular and cerebral outcome.…”