I read with great interest the article by Wigmore et al.1  at the Royal Marsden Hospital (London, United Kingdom), which suggested that total intravenous anesthesia (TIVA) is associated with improved cancer survival when compared to volatile inhalational anesthesia. The study has caused a great deal of excitement among many, and with good cause, demonstrating a 50% greater risk of mortality in the volatile group compared to TIVA.

I noticed that even after propensity matching, there was a statistically significant difference in transfusion rates between groups, there being an almost 50% higher rate of blood transfusion in the group receiving a volatile anesthetic (150 vs. 110 patients, P = 0.011). The reason for this difference is unclear; it may be that patients undergoing TIVA have lower rates of perioperative anemia, have less bleeding intraoperatively, or simply that anesthetists who use TIVA also have more conservative thresholds for blood transfusion.

It is recognized that conservative blood transfusion strategies may offer survival benefit,2  and reducing the use of allogenic blood transfusion may improve mortality.3  In fact, blood transfusion has been reported to worsen a variety of outcomes4  in cancer surgery including increasing incidence postoperative infections and increasing disease recurrence in addition to increasing mortality.4,5  Perioperative blood transfusion may influence immunomodulation in a number of ways,6  including potentiating postoperative levels of the cytokine interleukin-6 and interleukin-6–inducible tumor growth factors such as hepatocyte growth factor and vascular cell adhesion molecule 1.5  So potentially both blood transfusion and use of volatile may have contributed to reduce survival in the inhalational group via their impact on immunomodulation, thereby increasing cancer cell growth.

The magnitude of the TIVA survival benefit seen in the Royal Marsden study1  can clearly not be explained by the differences in transfusion rates alone. In absolute terms, there were 190 more deaths in the propensity-matched volatile group, but only 40 more patients in that group underwent blood transfusion. However, I believe differing transfusion rates between groups may be an important confounding factor, which was not mentioned by the authors in their discussion. It is increasingly recognized that many aspects of anesthetic care,7  including perioperative transfusion, use of opioid analgesia, and regional anesthesia, may all alter the immune response and influence cancer recurrence and thus survival. Clearly the situation is far more complex than the headline; I do hope when prospective research is undertaken, it takes these wide-ranging aspects of perioperative care into account.

The author declares no competing interests.

1.
Wigmore
TJ
,
Mohammed
K
,
Jhanji
S
:
Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: A retrospective analysis.
Anesthesiology
2016
;
124
:
69
79
2.
Hébert
PC
,
Wells
G
,
Blajchman
MA
,
Marshall
J
,
Martin
C
,
Pagliarello
G
,
Tweeddale
M
,
Schweitzer
I
,
Yetisir
E
:
A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion requirements in Critical Care Investigators, Canadian Critical Care Trials Group.
N Engl J Med
1999
;
340
:
409
17
3.
Goodnough
LT
,
Maggio
P
,
Hadhazy
E
,
Shieh
L
,
Hernandez-Boussard
T
,
Khari
P
,
Shah
N
:
Restrictive blood transfusion practices are associated with improved patient outcomes.
Transfusion
2014
;
54
(
10 pt 2
):
2753
9
4.
Miki
C
,
Hiro
J
,
Ojima
E
,
Inoue
Y
,
Mohri
Y
,
Kusunoki
M
:
Perioperative allogeneic blood transfusion, the related cytokine response and long-term survival after potentially curative resection of colorectal cancer.
Clin Oncol (R Coll Radiol)
2006
;
18
:
60
6
5.
Weber
RS
,
Jabbour
N
,
Martin
RC
II
:
Anemia and transfusions in patients undergoing surgery for cancer.
Ann Surg Oncol
2008
;
15
:
34
45
6.
Cata
JP
,
Wang
H
,
Gottumukkala
V
,
Reuben
J
,
Sessler
DI
:
Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions.
Br J Anaesth
2013
;
110
:
690
701
7.
Heaney
A
,
Buggy
DJ
:
Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis?
Br J Anaesth
2012
;
109
(
suppl 1
):
i17
28