Circulation 84,122 • Volume 24, No. 3 • Fall 2009   Issue PDF

Readers Explore Relationship of Anesthesia to Cancer Outcomes – Authors Offer Reply

Lee A. Balaklaw, MD; Peter H Norman, MD, FRCPC; Dilip R. Thakar, MD; Ronaldo V. Purugganan, MD; Antje Gottschalk, MD; Marcel Durieux, MD PhD; Mohamed Tiouririne, MD

To the Editor

In the winter 2009 APSF Newsletter, Dr. Durieux indicates in the lead article that based on the literature, general anesthetic agents depress immune function, and are implicated in increased cancer morbidity and mortality.

How long would general anesthetics depress immune function after an anesthetic is concluded?

Is this immune depression as brief as the anesthetic or a short time after that? If so, why would that brief duration of immune depression have significant ongoing impact on immune function, such that tumor growth would be enhanced and cancer morbidity and mortality increased?

Are the patients receiving general anesthesia for cancer surgery generally a more ill patient population to start with?

If so, could it be perhaps that such patients have a poorer preoperative prognosis anyway, such that the relationship between increased cancer related morbidity and mortality is associated with, but not caused by the general anesthetic?

I would appreciate Dr. Durieux answering these questions since they would aid in my and perhaps others’ understanding of the mechanisms involved in increased cancer-related morbidity and mortality after general anesthetics.

Lee A. Balaklaw, MD
Louisa, KY

To the Editor

We read with interest the article by Dr. Durieux in the Winter 2008-2009 APSF Newsletter. We are anesthesiologists at the UTMD Anderson Cancer Center in Houston and have recently published the results of our investigation of whether aprotinin decreased blood loss when employed for the operation of extrapleural pneumonectomy. This prospective, randomized and blinded study not only found that aprotinin, despite its current disfavor in cardiac surgery, decreased blood loss; it also significantly improved the survival of these mesothelioma patients. All investigators felt that publication in the cancer literature was preferable to the anesthesia literature due to the implications for treatment of cancer patients. Incidentally, this study also suggests that surgical and oncologic studies that do not control for anesthesia type may be incorrect in their results and interpretation. We are all members of UTMDACC’s Thoracic Anesthesia group and are cross-appointed to Thoracic and Cardiovascular Surgery.

Peter H Norman, MD, FRCPC
Dilip R. Thakar, MD
Ronaldo V. Purugganan, MD
Houston, TX

In reply:

We thank Drs. Balaklaw, Norman, Thakar, Purugganan, and Moss for their insightful comments on our article. As to the question regarding the duration of the immune suppression by anesthetics: their effect is likely to be brief (i.e., not exceeding by much the duration of administration). Effects of surgery on the immune response may last from hours to days, depending on the invasiveness of the procedure. However, it should be realized that even brief suppression may have long-term consequences. If transient inhibition of NK cell function allows a cancer cell, released during surgery, to find a foothold, or if several hours of decreased immune surveillance allows a micrometastasis to escape from control, this can have devastating eventual consequences. As emphasized by Dr. Moss, the effects of opiates on angiogenesis may be particularly damaging, and these drugs are commonly administered for days.

As to the issue of causality vs. association: in the largest retrospective studies demonstrating benefit of regional anesthesia, patients received regional anesthesia in addition to—not instead of—general anesthesia. But still, the question as to causality cannot be conclusively answered with the current data, since all of it is retrospective. Multivariate analysis of the retrospective studies attempts to compensate for possible confounders (such as the patients in one group being more sick than those in the other), but it cannot provide the same degree of confidence as a prospective, randomized, controlled trial can do. Several of such trials are in progress, but given the nature of the question, it will be years before we will have a definitive answer.

Antje Gottschalk, MD
Marcel Durieux, MD PhD
Mohamed Tiouririne, MD