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BMC Med Res Methodol. 2019 Jan 14;19(1):17. doi: 10.1186/s12874-019-0660-9.

The triple variable index combines information generated over time from common monitoring variables to identify patients expressing distinct patterns of intraoperative physiology.

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Department of Anesthesiology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
Department of Biomedical Informatics, University of Pittsburgh, 5607 Baum Boulevard, Pittsburgh, PA, 15206, USA.
Departments of Philosophy and Psychology, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
Department of Anesthesiology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
Department of Critical Care Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.



Mean arterial pressure (MAP), bispectral index (BIS), and minimum alveolar concentration (MAC) represent valuable, yet dynamic intraoperative monitoring variables. They provide information related to poor outcomes when considered together, however their collective behavior across time has not been characterized.


We have developed the Triple Variable Index (TVI), a composite variable representing the sum of z-scores from MAP, BIS, and MAC values that occur together during surgery. We generated a TVI expression profile, defined as the sequential TVI values expressed across time, for each surgery where concurrent MAP, BIS, and MAC monitoring occurred in an adult patient (≥18 years) at the University of Pittsburgh Medical Center between January and July 2014 (n = 5296). Patterns of TVI expression were identified using k-means clustering and compared across numerous patient, procedure, and outcome characteristics. TVI and the triple low state were compared as prediction models for 30-day postoperative mortality.


The median frequency MAP, BIS, and MAC were recorded was one measurement every 3, 5, and 5 min. Three expression patterns were identified: elevated, mixed, and depressed. The elevated pattern displayed the highest average MAP, BIS, and MAC values (86.5 mmHg, 45.3, and 0.98, respectively), while the depressed pattern displayed the lowest values (76.6 mmHg, 38.0, 0.66). Patterns (elevated, mixed, depressed) were distinct across the following characteristics: average patient age (52, 53, 54 years), American Society of Anesthesiologists Physical Status 4 (6.7, 16.1, 27.3%) and 5 (0.1, 0.6, 1.6%) categories, cardiac (2.2, 6.5, 16.1%) and emergent (5.8, 10.5, 12.8%) surgery, cardiopulmonary bypass use (0.3, 2.6, 9.8%), intraoperative medication administration including etomidate (3.0, 7.3, 12.6%), hydromorphone (47.6, 26.3, 25.2%), ketamine (11.2, 4.6, 3.0%), dexmedetomidine (18.4, 16.6, 13.6%), phenylephrine (74.0, 74.8, 83.0), epinephrine (2.0, 6.0, 18.0%), norepinephrine (2.4, 7.5, 21.2%), vasopressin (3.4, 7.6, 21.0%), succinylcholine (74.0, 69.0, 61.9%), intraoperative hypotension (28.8, 33.0, 52.3%) and the triple low state (9.4, 30.3, 80.0%) exposure, and 30-day postoperative mortality (0.8, 2.7, 5.6%). TVI was a better predictor of patients that died or survived in the 30 days following surgery compared to cumulative triple low state exposure (AUC 0.68 versus 0.62, p < 0.05).


Surgeries that share similar patterns of TVI expression display distinct patient, procedure, and outcome characteristics.


Bispectral index; Intraoperative monitoring; K-means clustering; Mean arterial pressure; Minimum alveolar concentration; Perioperative medicine; Postoperative death; Triple low state; Triple variable index; Unsupervised machine learning

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