We read with great interest the recent article by Sessler et al. ,1which suggested that a “triple low” of mean arterial pressure, bispectral index, and minimum alveolar concentration strongly predict postoperative mortality. We would like to congratulate them on their excellent and impressive study on this important subject. However, there are a few important points we wish to comment on.

The authors reported that triple low had four times the hazard of death within 30 days compared with patients who did not have a triple low after adjusting for patient age, sex, comorbidities, and surgical complexity. The following question arises: is intraoperative triple low an independent risk predictor or just a marker of hazard level of postoperative mortality? In fact, the results properly account for inherent variability in risk associated with differences in baseline characteristics (or severity of preexisting diseases) as well as differences in procedural complexity between patients with triple low and those without. From our perspective, it may be extrapolated that patients with triple low have more preoperative risk factors in comparison with those without. However, the authors did not analyze these differences between patients with triple low and those without. In addition, the inclusion of other perioperative risk factors in the multivariate analyses may increase the likelihood of identifying the independent association of intraoperative triple low and postoperative outcomes. Although the authors attempted to control for patient comorbidities and procedural risk using their recently published Risk Stratification Index,2,3some important intra- and postoperative risk factors (e.g ., intraoperative blood transfusion and postoperative troponin T level) were not included in the multivariate analyses. Intraoperative blood transfusion was associated with an increased risk of 30-day mortality in patients undergoing noncardiac surgery.4The postoperative troponin T level after surgery was significantly associated with mortality among patients undergoing noncardiac surgery.5,6Moreover, triple low may offer an accurate characterization of patient risk contributing to mortality in the postoperative period when combined with other perioperative risk factors. Meanwhile, it would also be of essence to know the relationship between preoperative risk factors and the occurrence of intraoperative triple low. In this way, we might be able to identify patients with high-risk levels preoperatively, who could receive intensive perioperative management to limit postoperative mortality.

However, adverse effects of intraoperative hypotension perhaps are related more to the cause of the hypotension (e.g ., hypovolemia, myocardial dysfunction, sepsis, or anesthetic overdose) than to the arterial blood pressure per se .7Similarly, intraoperative cerebral state (e.g. , cerebral hypoxia or increased cerebral susceptibility to the effects of anesthetics), not low bispectral index and minimum alveolar concentration per se , is associated with adverse outcomes after surgery.7Thus, it is unclear whether triple low results in the increased risk of postoperative mortality or simply detects patients with potential high risk of death. In our opinion, triple low may simply reflect severity of the patient’s underlying disease and serve as a marker of high risk of postoperative mortality, and indeed is attributable to the multiple preoperative risk factors the patient suffers from simultaneously. It is rational to consider that specific groups of patients may be more likely to exhibit or be affected by triple low, and this would warrant further subgroup analyses. However, the authors did not stratify patients into high-risk and low-risk groups based on the number of preexisting risk factors.

As mentioned by Drs. Kheterpal and Avidan in their accompanying Editorial, short-term 30-day mortality was the primary outcome, which increases the possibility of a causal contribution of intraoperative events.8The authors also did not identify the causes of death, but based on a recent study, a substantial proportion of deaths are likely to be related to cardiovascular causes.5It is essential that the sensitivity analysis of triple low, associated with different causes of death, should be performed.

The association of a triple low of mean arterial pressure, bispectral index, and minimum alveolar concentration with postoperative mortality in noncardiac surgical patients is a fascinating topic, and this impressive study is highly important for our understanding of this interesting phenomenon. Therefore, additional clinical trials are needed to confirm the prognostic value of triple low and establish whether interventions can alter patients’ risk of death based on triple low events during surgery.

Sessler DI, Sigl JC, Kelley SD, Chamoun NG, Manberg PJ, Saager L, Kurz A, Greenwald S. Hospital stay and mortality are increased in patients having a “triple low” of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia. ANESTHESIOLOGY. 2012;116:1195–203
Sessler DI, Sigl JC, Manberg PJ, Kelley SD, Schubert A, Chamoun NG. Broadly applicable risk stratification system for predicting duration of hospitalization and mortality. ANESTHESIOLOGY. 2010;113:1026–37
Dalton JE, Kurz A, Turan A, Mascha EJ, Sessler DI, Saager L. Development and validation of a risk quantification index for 30-day postoperative mortality and morbidity in noncardiac surgical patients. ANESTHESIOLOGY. 2011;114:1336–44
Glance LG, Dick AW, Mukamel DB, Fleming FJ, Zollo RA, Wissler R, Salloum R, Meredith UW, Osler TM. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. ANESTHESIOLOGY. 2011;114:283–92
Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf SVascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators. . Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307:2295–304
Levy M, Heels-Ansdell D, Hiralal R, Bhandari M, Guyatt G, Yusuf S, Cook D, Villar JC, McQueen M, McFalls E, Filipovic M, Schünemann H, Sear J, Foex P, Lim W, Landesberg G, Godet G, Poldermans D, Bursi F, Kertai MD, Bhatnagar N, Devereaux PJ. Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: A systematic review and meta-analysis. ANESTHESIOLOGY. 2011;114:796–806
Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg. 2005;100:4–10
Kheterpal S, Avidan MS. “Triple low”: Murderer, mediator, or mirror. ANESTHESIOLOGY. 2012;116:1176–8