Anesth Analg 2005;101:1880
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000180253.16926.83
LETTER TO THE EDITOR
The Evidence That Deep Anesthesia Impacts Long Term Mortality Is Not Compelling
Jeremy Scarlett, MD,
Nathan Hahn, MD,
Eric Jacobsohn, MD, and
Michael S. Avidan, MD
Washington University School of Medicine, Saint Louis, MO, scarletj{at}msnotes.wustl.edu
To the Editor:
Monk et al. suggested following an observational study that anesthetic management may affect mortality 1 yr after noncardiac surgery (1). In particular, they hypothesized that increased cumulative deep hypnotic time may be associated with increased 1-yr mortality (1). We have several concerns in relation to this study’s design, data analysis, and conclusions.
The authors assert, "Monitoring of hypnotic depth is now possible using digital signal processing techniques applied to the electroencephalogram" (1). This is a controversial assertion. In fact, even the article that the authors cite to support this reported the relationship between the Bispectral Index (BIS) and loss of consciousness—not anesthetic depth—in volunteers without surgery (2). There is no compelling evidence that the BIS monitor, or any other similar monitor, is a reliable indicator of anesthetic depth.
Even if we accept the authors’ premise that the BIS provides an accurate measurement of anesthetic depth, it is still not clear why they chose the arbitrary BIS value of 45 for their threshold defining "deep hypnotic time." The authors justify this value by citing an article (3) that was not designed to address the relationship between BIS and anesthetic depth. The article reported on the possible usefulness of BIS in facilitating rapid emergence and recovery (3). In an abstract published in 2002 (4) by some of the same authors of this current study (1), deep anesthesia was defined as an arbitrary BIS value less than 40 (4).
We think that the method chosen to calculate deep hypnotic time in the present study (1) was not optimal. The authors did not calculate a time average value (i.e., area under the curve). Instead they merely calculated the time that the BIS was below the arbitrary cut-off of 45 (1). If one patient spent 30 min under general anesthesia with an arbitrary BIS value of 44 and a second patient spent 10 min with an arbitrary BIS value of 46 and 20 min with an arbitrary BIS value of 10, the first patient would have received a "deeper" anesthetic by the authors’ criteria.
We question the authors’ omission of drugs proven to decrease (long-term) postoperative mortality such as ß adrenergic-blockers (5), clonidine (6), and statins (7) from their multivariate analysis. These could conceivably have been powerful confounders. Beta-adrenergic blockers not only decrease postoperative mortality, they also decrease intraoperative BIS values (8).
In the Discussion section of the article the authors invoke several theories attempting to link anesthesia to mortality via alterations in the inflammatory cascade (1). However, the majority (51.7%) of their subjects’ deaths were attributable to cancer. We question the biological plausibility of 1.1 h of a deep anesthetic having an effect on the progression of a fatal cancer over a 12-mo period. Even the authors seem to discard this hypothesis later in their discussion when they instead attempt to implicate "cerebral hypoxia or increased cerebral susceptibility to the effects of anesthetics" (1) as factors causing increased mortality.
Finally, as the authors disclosed, the statistician for this research was an employee of Aspect Medical Systems, the manufacturers and marketers of BIS technology. This introduces a conflict of interests and a source of potential bias that could have been avoided by choosing an independent statistician.
References
- Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg 2005;100:4–10.[Abstract/Free Full Text]
- Glass PS, Bloom M, Kearse L, et al. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997;86:836–47.[Web of Science][Medline]
- Gan TJ, Glass PS, Windsor A, et al. Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. Anesthesiology 1997;87:808–15.[Web of Science][Medline]
- Weldon BC, Mahla ME, van der Aa MT, Monk T. Advancing age and deeper intraoperative anesthetic levels are associated with higher first year death rates (abstract). Anesthesiology 2002;96:A1097.
- Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996;335:1713–20.[Abstract/Free Full Text]
- Wallace AW, Galindez D, Salahieh A, et al. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology 2004;101:284–93.[Web of Science][Medline]
- Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 2003;107:1848–51.[Abstract/Free Full Text]
- Menigaux C, Guignard B, Adam F, et al. Esmolol prevents movement and attenuates the BIS response to orotracheal intubation. Br J Anaesth 2002;89:857–62.[Abstract/Free Full Text]
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