Radiol Oncol 2024; 58(1): 9-14. doi: 10.2478/raon-2024-0012
9
review
The influence of anaesthesia on cancer growth 
Iztok Potocnik
1,2
, Milena Kerin-Povsic
1
, Jasmina Markovic-Bozic
2,3
1
 Department of Anaesthesiology and Intensive Care, Institute of Oncology Ljubljana, Ljubljana, Slovenia
2
 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
3
 Department of Anaesthesiology and Surgical Intensive Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia 
Radiol Oncol 2024; 58(1): 9-14.
Received 10 September 2023 
Accepted 22 November 2023
Correspondence to: Assit. Prof. Iztok Potočnik, M.D., Ph.D., Department of Anaesthesiology and Intensive Care, Institute of Oncology 
Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia. E-mail: vpotocnik@onko-i.si
Iztok Potocnik and Jasmina Markovic-Bozic conribuded equally to this work.
Disclosure: No potential conflicts of interest were disclosed.
This is an open access article distributed under the terms of the CC-BY license (https://creativecommons.org/licenses/by/4.0/).
Background. Oncological patients make up a large proportion of all surgical patients. Through its influence on the 
patient’s inflammatory and immune system, the choice of anaesthetic technique has an indirect impact on the 
health of the individual patient and on public health. Both the specific and the non-specific immune system have 
a major influence on the recurrence of carcinomas. The pathophysiological basis for growth and metastasis after 
surgery is the physiological response to stress. Inflammation is the organism’s universal response to stress. Anaesthetics 
and adjuvants influence perioperative inflammation in different ways and have an indirect effect on tumour growth 
and metastasis. In vitro studies have shown how individual anaesthetics influence the growth and spread of cancer, 
but clinical studies have not confirmed these results. Nevertheless, it is advisable to use an anaesthetic that has shown 
lesser effect on the growth of cancer cells in vitro.
Conclusions. In this review, we focus on the area of the effects of anaesthesia on tumour growth. The field is still 
relatively unexplored, there are only few clinical prospective studies and their results are controversial. Based on the 
review of new research findings we report on recommendations about anaesthetics and anaesthetic techniques that 
might be preferable for oncological surgical procedures. 
Key words: cancer growth; anaesthesia; inflammation
Introduction
Perioperative morbidity and mortality have de-
creased over time due to the use of modern anaes-
thesia and surgical techniques. The question arises 
as to how we can influence long-term morbidity 
and mortality in cancer patients. Published stud-
ies have shown that an appropriate anaesthetic 
technique (AT) can influence the recurrence and 
spread of the disease.
1,2
 Oncological patients make 
up a large proportion of all surgical patients, and 
their number increases by more than 25% every 
five years. Two thirds of all cancer patients require 
at least one operation during treatment. Therefore, 
the choice of AT has an indirect impact on the 
health of the individual patient and on public 
health.
1,2
Metastases develop because cancer cells evade 
the immune system, multiply, and spread to other 
tissues and organs.
3
 It has been shown that anaes-
thesia influences the spread of cancer through the 
immune system.
1,2
 Both specific and non-specific 
immune systems have a major influence on metas-
tasis.
1,2
 During the perioperative period, the organ-
ism is exposed to many processes that can affect 
the metastasis. The most important of these are 
inflammation, anaesthetics, hypothermia and the 
transfusion of blood products.
1-3
Pathophysiology of metastasis
The pathophysiological basis for the growth and 
metastasis of carcinomas after surgery is the reac-

Radiol Oncol 2024; 58(1): 9-14.
Potocnik I et al. / Anaesthesia and cancer growth 10
tion to stress. The universal reaction of the organ-
ism to stress is inflammation. The organism reacts 
to all harmful stimuli with inflammation. During 
an operation, both the systemic inflammatory re-
action and the ischaemia/reperfusion reaction are 
triggered.
4
 In addition, severe tissue damage oc-
curs, which is also a cause of the stress reaction 
and inflammation. Inflammatory factors such as 
interleukins (ILs) and prostaglandins (PGs) are 
released into the bloodstream as a result of the 
non-specific inflammatory response. To a certain 
extent, they have the task of protecting the organ-
ism from harmful stimuli, but if the reaction is too 
strong, additional tissue damage occurs. 
When inflammation escalates a vicious circle 
may be triggered. The most important inflamma-
tory factors that are released and influence the 
growth of tumour cells are interleukin-6 (IL-6) 
and prostaglandin E2 (PGE2).
5
 These factors in-
fluence the reduced activity of natural killer cells, 
so that cellular immunity is weakened, and the 
tumour cells can evade the immune system and 
multiply. As a result of immunosuppression, cer-
tain hormones (catecholamines, PGs and growth 
factors) are released, which also influence the 
growth and metastasis of carcinomas. Tumour 
cells have mechanisms to increase their insensi-
tivity to hypoxia. Due to tissue hypoxia, certain 
genes are expressed in tumour cells. Hypoxia in-
ducible factor 1-alpha (HIF-1α) is released, which 
promotes angiogenesis, proliferation, and metas-
tasis. High HIF-1α levels are a predictive factor for 
long-term morbidity and mortality due to postop-
erative carcinoma growth.
6
The impact of inflammation on 
metastasis
Inflammation is a universal physiological defence 
reaction of the organism that protects the body 
from harmful factors. It is triggered by the activa-
tion of the immune system and causes the elimi-
nation of harmful stimuli, prevents the spread of 
damage and repairs the affected tissue. It involves 
several reactions: vascular reaction (vasodilatation, 
exudation), cellular reaction (migration, adhesion, 
phagocytosis, degranulation) and connective tis-
sue reaction (matrix formation, repair, angiogene-
sis).
4,6,7
 A distinction is made between non-specific 
and specific immunity: non-specific immunity is 
characterised by various cascade reactions and the 
production of inflammatory factors such as pros-
taglandins and cytokines. The product of specific 
immunity are antibodies that are directed pre-
cisely against a specific harmful stimulus such as 
carcinoma cells. Cellular immunity also includes 
natural killer cells, which ensure the death of 
harmful cells (tumour cells, bacteria, blood cells in 
transfusion derivatives).
5,6
 Both forms of specific 
immunity function and communicate with each 
other via signalling molecules. A harmful cell la-
belled with antibodies is easy prey for the natural 
killer cells. The inflammatory reaction must be 
precisely regulated.
4,6,7
 An excessive inflammatory 
response also damages the body’s own tissue and 
causes postoperative complications. An excessive 
reaction is referred to as a systemic inflammatory 
response (SIRS).
7
 
An inflammatory reaction is also triggered by 
tissue damage during the operation.
8
 Inflammation 
may promote the postoperative growth of any re-
sidual tumour and progression of metastasis.
4,6
 
Therefore, the least possible invasive surgical 
technique should be used. There are three harm-
ful perioperative reactions triggered by inflam-
mation.
8,9
 The first harmful reaction is SIRS. The 
inflammatory event involves the entire organism. 
Many cytokines are released because their regula-
tory level is disturbed.
7-11
 In severe inflammation, 
SIRS can lead to organ dysfunction and organ fail-
ure. SIRS complications include acute lung injury 
(ALI), acute renal failure (ARF), shock and multi-
ple organ failure (MOF).
10,11
The second harmful reaction is the ischaemia/
reperfusion reaction. When ischaemic tissue is 
reperfused, large amounts of reactive oxygen spe-
cies (ROS) are released. If they are not neutralised 
and removed, they can cause tissue damage. The 
enzyme xanthine oxidase (XOX) plays an impor-
tant role in this reaction. During ischaemia, it is 
formed in large quantities by the enzyme xanthine 
dehydrogenase (XDH) and breaks down purines. 
XOX remains inactive until sufficient oxygen is 
available. This happens when the tissue is supplied 
with blood again.
7-11
 In addition, during ischaemia 
there is a decrease in the regeneration of adenosine 
triphosphate (ATP) from adenosine diphosphate 
(ADP). Due to the lack of oxygen, ADP is also re-
duced to adenosine monophosphate (AMP) in or-
der to generate additional energy.
7
 After reperfu-
sion and replenishment of the tissue with oxygen, 
XOX is activated, and part of the AMP is degraded 
to uric acid. During this process, electrons are re-
leased and transferred to oxygen to form ROS. If 
the ROS scavengers are unable to remove these, 
nearby cells are damaged, and an inflammatory 
reaction is triggered. It is initially localised, but if 
severe enough, it leads to SIRS.
7

Radiol Oncol 2024; 58(1): 9-14.
Potocnik I et al. / Anaesthesia and cancer growth 11
The third adverse perioperative reaction is 
called acute lung injury (ALI) and acute respira-
tory distress syndrome (ARDS). ARDS leads to cy-
tokine release, damage to the pulmonary vascular 
endothelium, decreased surfactant production and 
alveolar surface tension, fluid accumulation and 
fibrosis. The mortality rate for ARDS is 20-50%.
7-11
The effect of anaesthetics and 
anaesthetic technique on inflammation 
and metastasis
The choice of anaesthetic and adjuvants primarily 
influences perioperative inflammation in various 
ways and has indirect effects on tumour growth 
and metastasis.
12
 
Rational anaesthesia management has a ma-
jor influence on the long-term surgical outcome.
4
 
Anaesthetics affect the non-specific and specific 
inflammatory response, the immune cascades 
and consequently the production of cytokines and 
the function of inflammatory cells.
13
 For example, 
propofol increases the number of killer cells but 
reduces their cytotoxic activity, while sevoflurane 
increases the number of killer cells but reduces the 
number and activity of other immune cell types 
such as CD4 T- helper and CD-8 cytotoxic T- lym-
phocytes. The overall effect on the immune system 
and inflammation may depend on many factors, 
including the specific combination and dose of an-
aesthetic agents used.
13
A single agent lowers the level of some cytokines 
and increases the level of others. Some cytokines 
are pro-inflammatory (TNFα, IL-1, IL-6, IL-8), 
while others are anti-inflammatory (IL-10). This 
further complicates the effect of cytokines. Studies 
have shown that cytokine levels in the blood in-
crease immediately after induction of anaesthesia 
and even before surgery.
14
 Opioids reduce the in-
flammatory response because they reduce intra-
cellular cyclic AMP, which is an important factor 
in stimulating IL-6 synthesis.
15
 In addition, neu-
trophils have opioid receptors on their membrane 
that inhibit their function.
16
Pain also alters the immune response by in-
creasing the number of activated lymphocytes and 
decreasing the number of inhibitory T cells and T 
helper cells. Inflammatory processes are particu-
larly strongly activated in chronic pain.
17,18
 
Studies have shown that intravenous anaes-
thetics stimulate inflammatory cells to produce 
cytokines.
19
 Intravenous anaesthetics inhibit the 
polarisation and chemotaxis of neutrophils to a 
greater extent than volatile anaesthetics (VA).
20
 
Anaesthetics also influence proliferation, lympho-
cyte count and perioperative immunoglobulin lev-
els in the blood.
21,22
 In addition to the choice of an-
aesthetic, different regional techniques (epidural, 
paravertebral anaesthesia) also influence periop-
erative inflammation depending on the anaesthet-
ics used.
23,24
Transfusion of blood derivatives reduces the 
number of T-cytotoxic leukocytes, TNF production 
and macrophage chemotaxis.
25
Finally, the central nervous system also has an 
effect on perioperative stress and the immune re-
sponse, which is the subject of psychoneuroimmu-
nology.
26,27
 Thoughts and emotions also influence 
the immune system via centres in the brain. The 
hypothalamus plays a central role because it influ-
ences the sympathetic nervous system and the hy-
pothalamic-pituitary-adrenal axis by altering cat-
echolamine levels, corticosteroids, and opioids in 
the body.
27
 The concentration of growth hormone 
and prolactin in the blood also changes.
28
 All these 
processes have a significant influence on the func-
tion of the immune system. The immune system is 
inhibited and weakened in a stressful situation.
29
There are not many clinical, randomised stud-
ies that have investigated the direct influence of 
AT on tumour growth and metastasis after sur-
gery. The results are often controversial. The stud-
ies published in recent years have not shown any 
advantages of different AT such as regional, gen-
eral, or combined anaesthesia.
30-33
VA modulate the inflammatory response and 
have a positive anti-inflammatory effect.
34,35
 
However, it is not clear whether this also has a 
negative effect on tumour cells. There are obser-
vations that they have a pro-inflammatory effect 
and therefore accelerate metastasis. The molecu-
lar mechanism of this process is not known.
36
 In 
vitro, they have shown a mild anti-inflammatory 
and thus protective effect, while increased levels 
of HIF-1α have been observed in vivo.
4,7
 VA are 
thought to cause chemoresistance and attenuate 
the effect of adjuvant chemotherapy.
1,2
 In vitro, 
sevoflurane has been shown to promote inflam-
mation via the nuclear factor kappa B (NF- κB) 
pathway.
37
Propofol is known to have an anti-inflammato-
ry effect, particularly in the central nervous sys-
tem, where it prevents perioperative neuroinflam-
mation.
35,38
 Propofol acts in the cell nucleus and 
influences the formation of NF- κB. In vitro studies 
have also shown an effect on the transcription of 
ribonucleic acid (RNA) as well as anti-inflamma-
tory and antioxidant effects. The antitumour effect 

Radiol Oncol 2024; 58(1): 9-14.
Potocnik I et al. / Anaesthesia and cancer growth 12
of propofol has not yet been confirmed with cer-
tainty, but it lowers HIF-1α levels.
1-3
 However, in 
triple-negative breast cancer cell lines, propofol in-
creased the antitumour effect of doxorubicin and 
paclitaxel.
39
 However, clinical studies have shown 
very controversial results.
39
According to published studies, ketamine and 
thiopental have a major impact on inflammation. 
They influence the function of the immune system 
by inhibiting NK cells.
1-3
 Ketamine also increases 
the level of anti-apoptotic protein.
2,3
Anaesthesiologist is faced with the dilemma of 
whether to anaesthetise a carcinoma patient with 
total intravenous anaesthesia (TIVA) or with vola-
tile induced and maintained anaesthesia (VIMA). 
Several studies have confirmed the anti-inflam-
matory effect of VA. In cardiac surgery, pre- and 
post-conditioning are used due to the proven anti-
inflammatory and tissue-protective effect.
40
 The 
positive effect of sevoflurane has also been dem-
onstrated in liver surgery, where a strong inflam-
matory reaction is expected.
41,42
 It is also frequently 
used in intensive care medicine to sedate patients. 
It has been shown to have positive effects on the 
systemic inflammatory response of the organism 
and works very well in ARDS.
43
 It is also used in 
lung surgery. During lung surgery, several reac-
tions are triggered that lead to an excessive inflam-
matory response. Perioperative unilateral lung 
ventilation triggers an ischaemia/reperfusion re-
action, which can cause additional damage to the 
lungs already mechanically damaged by the op-
eration. Sevoflurane reduces the concentration of 
pro-inflammatory factors. Therefore, lung damage 
is also reduced, and fewer postoperative complica-
tions occur.
9,44
 Other studies have shown the pro-
inflammatory effect of VA.
45,46
 From this it could 
be concluded that they cause the progression of 
cancer, but clinical studies have not confirmed this 
with certainty. 
A recent meta-analysis of TIVA versus VA 
showed that 7,866 patients with breast, oesopha-
geal or non-small lung cancer had improved re-
currence-free survival after VIMA. In addition, 
studies that included 18,778 patients showed that 
overall survival was longer after VIMA than after 
T I VA.
47
 However, there were no differences be-
tween the two techniques in terms of the presence 
of circulating tumour cells in breast cancer pa-
tients.
48
 Furthermore, there were no effects on im-
mune cells and cancer-regulating factors between 
the two AT in colorectal cancer surgery.
45
The use of regional anaesthesia indirectly re-
duces the progression of cancer by decreasing the 
neuroendocrine response to surgery and reducing 
the use of opioids and VA.
49
 In addition, recently 
published and ongoing studies suggest a highly 
beneficial direct effect of local anaesthetics on 
carcinoma.
50-52
 Intraoperative intravenous lido-
caine infusion has been associated with reduced 
intraoperative opioid use and improved overall 
survival in patients undergoing pancreatic cancer 
surgery.
53
Opioids have been shown to have an unfavour-
able effect on tumour growth in vitro.
54-56
 Several 
clinical studies have been published and show a 
complex relationship that depends on many fac-
tors, such as the type of opioid, the amount of opi-
oid administered and adjuvants. The results of the 
studies are highly controversial but tend to favour 
a harmful effect of opioids.
44,55
 The different find-
ings on the cancer risk of opioids are a line of re-
search that needs to be pursued as they have major 
implications for clinical practise given the impor-
tance of opioid use in anaesthetic practice and pain 
management.
The exception is tramadol, which is supposed 
to protect the body against metastases. It does not 
inhibit the immune system like other opioids.
57
 
Unfortunately, tramadol is rarely used in oncology 
due to its weak analgesic effect and unpleasant 
side effects at higher doses.
There are also some studies in the field of an-
aesthetic adjuvants such as dexmedetomidine 
and clonidine. In vitro results indicated their un-
favourable effect on the growth and spread of 
cancer,
 
but clinical studies have not confirmed 
it.
58-60
 Studies have shown that dexmedetomidine 
has a positive effect on patients anaesthetised 
with sevoflurane, possibly because it reduces 
neuroinflammation.
61
 However, further studies 
are needed in this area.
However, there are also some studies on the 
use of other agents. Nonsteroidal anti-inflam-
matory drugs have potential anticancer effects.
62
 
Beta-blockers affect cancer growth and spread 
by reducing the sympathetic stress response.
63
 
Dexamethasone reduces inflammation and the 
immune response by inhibiting NK cells and thus 
has an unfavourable effect, but low antiemetic dos-
es are not thought to increase cancer growth and 
spread.
64
 Oxygen causes ROS synthesis and oxida-
tive stress and can induce various degrees of par-
tial to complete transformation from epithelium to 
mesenchyme in cancer cells. Even if the primary 
tumours are surgically removed, the effects of hy-
peroxia on micrometastases and circulating cancer 
cells may promote cancer progression or recur-

Radiol Oncol 2024; 58(1): 9-14.
Potocnik I et al. / Anaesthesia and cancer growth 13
rence. Therefore, it is necessary to use the lowest 
sufficient concentrations of oxygen.
65  
Conclusions
Recent studies have shown that anaesthesia may 
play an important role in the growth and spread 
of cancer. Volatile anaesthetics have proinflam-
matory effects and can therefore accelerate me-
tastasis. Propofol has an anti-inflammatory and 
antioxidant effect, causes less neuroinflammation 
and may have an antitumour effect. Regional an-
aesthesia plays an important role in reducing the 
likelihood of metastasis after surgery, as local an-
aesthetics have a protective effect on cancer recur-
rence. Opioids, except for tramadol, can accelerate 
cancer growth and spread and should be avoided 
or reduced perioperatively. Dexmedetomidine has 
no effect on the tumour, although it modulates in-
flammation.
In summary, there are still no clear answers to 
questions about the carcinogenicity of agents and 
techniques used during anaesthesia. The field 
needs further research.
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