British Journal of Anaesthesia 107 (S1): i90i95 (2011)

doi:10.1093/bja/aer340

REGIONAL ANAESTHESIA

Does regional anaesthesia really improve outcome?

S. C. Kettner, H. Willschke and P. Marhofer*
Department of Anaesthesia, Intensive Care Medicine and Pain Therapy, Medical University of Vienna, A-1090 Vienna, Austria
* Corresponding author. E-mail: peter.marhofer@meduniwien.ac.at

Editors key points

Outcome studies showing
differences in mortality between
regional and general anaesthetic
techniques are probably impossible.

Keywords: economy; outcome; regional anaesthesia

In 1987, Yeager and colleagues showed a dramatically reduced

mortality by epidural analgesia in high-risk surgical patients. In
2000, Rodgers and colleagues published an extensive
meta-analysis showing a reduction in postoperative mortality
and morbidity with neuraxial anaesthesia with the subsequent
recommendation of more widespread use of neuraxial anaesthesia. As in all fields of medicine, evidence in regional anaesthesia is rapidly growing. It is hard to review all relevant
studies, and therefore meta-analyses are very helpful to categorize the available evidence. Although the popularity of
meta-analyses has increased dramatically over the last two
decades, many are poorly conducted, the results are sometimes
questionable, and interpretation can lead to deceptive results.1
Evidence-based medicine has limitations, and some medical
questions can simply not be answered by randomized controlled
trials. Perhaps, it is an unrealistic expectation that regional
anaesthesia influences perioperative mortality. With estimated
anaesthesia-related mortality as low as 8.2 per million hospital
surgical discharges, it might be impossible to detect differences
in mortality in randomized controlled trials that would have to
include millions of patients. The Cochrane collaboration has published strict rules for meta-analyses,2 often resulting in differing
conclusions of Cochrane meta-analyses compared with
meta-analyses published in other journals. The following
review discusses the influence of various regional anaesthetic
techniques on outcome parameters. Given the high quality of
the Cochrane collaboration, we will consider Cochrane analyses
as the best available evidence in this review.

Peripheral nerve blocks

Consideration of the various techniques of peripheral nerve
blocks and potential advances in comparison with general

anaesthesia requires a short discussion of the safe and effective performance of peripheral nerve block. Peripheral nerve
blocks and local anaesthesia have very few cardiovascular or
pulmonary side-effects. There are still potential complications,
and peripheral nerve block must be done with adequate safety
precautions by anaesthetists with appropriate experience. In
rare cases, such as accidental block of the phrenic nerve
during interscalene brachial plexus block, nerve blocks can
compromise pulmonary function, usually without clinical consequences.3 A potentially significant side-effect is systemic
toxicity of local anaesthetics.4 With ultrasound guidance, the
volumes of injected local anaesthetics can be decreased dramatically,5 8 limiting the risk of toxic side-effects.
In experienced hands, it seems likely that peripheral nerve
block would be safer than general anaesthesia due primarily
to the avoidance of airway management. However, evidence
to prove this assumption will never be available due to the
low numbers of severe anaesthesia-related complications.
Nevertheless, perioperative opioid consumption can be
reduced or even avoided, in particular with peripheral perineural catheter techniques.9 Subsequently, opioid-related
side-effects can be reduced when perineural block is performed. Optimal performance of single-shot or continuous
perineural block is the major prerequisite for implementation
of these techniques in daily clinical practice.

Epidural anaesthesia
Postoperative epidural analgesia after major abdominal and
thoracic surgery has been extensively investigated. However,
most of the studies did not include enough patients for definitive conclusions. Accordingly, a number of meta-analyses
have addressed the question whether and which outcome

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Meta-analyses have shown

improved outcomes for specific
endpoints associated with specific
regional anaesthesia techniques.

Summary. In recent decades, a number of studies have attempted to determine

whether regional anaesthesia offers convincing benefits over general
anaesthesia. However, today we interpret meta-analyses more carefully, and it
remains unclear whether regional anaesthesia reduces mortality. However,
regional anaesthesia offers superior analgesia over opioid-based analgesia,
and a significant reduction in postoperative pain is still a worthwhile outcome.
Recent developments in technical aspects of regional anaesthesia have the
potential to provide significant advantages for many patients in all age groups.
Moreover, studies focusing on specific outcomes have shown benefits for
regional anaesthesia used for surgery and postoperative analgesia.

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Regional anaesthesia and outcome

Spinal anaesthesia
Spinal anaesthesia is the preferred anaesthetic method for
sub-umbilical surgery, particularly in elderly patients and
parturients. While insufficient data are available for obstetric
anaesthesia, a large number of studies have attempted to
establish the best evidence for neuraxial anaesthesia for
various surgical procedures, mainly in elderly patients.
Parker and colleagues16 investigated in a Cochrane
meta-analysis 22 clinical trials involving 2567 patients
where neuraxial (mainly spinal) anaesthesia was compared
with general anaesthesia. Despite the fact that all included

trials had methodical problems, the authors found a

reduced risk for postoperative deep venous thrombosis
(30% compared with 47%) and acute postoperative confusion (9.4% compared with 19.2%) in patients treated with
neuraxial (mainly spinal) anaesthesia compared with
general anaesthesia. There was no evidence for reduced perioperative mortality or other outcome parameters (myocardial infarction, pulmonary embolism, etc.).
Luger and colleagues17 investigated 18 715 patients from
34 randomized controlled trials in which spinal anaesthesia
was compared with general anaesthesia for hip surgery in
elderly patients. Their conclusions are much more optimistic
compared with the Cochrane meta-analysis above with a
clear statement to use regional (spinal) anaesthesia for hip
surgery in elderly patients. Contrary to other publications,
Luger and colleagues highlight the individual decision
process and the multi-disciplinary approach for optimal
treatment of these patients.

Regional anaesthesia and specific outcome

parameters
The following chapter describes possible positive influences
of regional anaesthesia on various particular outcome parameters, which is summarized in Table 1.

Anti-inflammatory effects
Possible mechanisms of anti-inflammatory effects after
regional anaesthesia include C-fibre block,18 reduced cytokine production,19 and block of sympathetic nerve activity.20
Since postoperative pain is mainly caused by tissue inflammation and C-fibre activation, reduced cytokine production
might limit the inflammatory response after surgery21 23
and the severity of postoperative pain. Cytokines can also
influence the development of postoperative hyperalgesia.24
Martin and colleagues25 recently investigated the possible
anti-inflammatory effects of peripheral nerve block after
major knee surgery. They showed that combined sciatic
and femoral nerve block reduced clinical inflammation (evaluated by local skin temperature and circumference of the
knee) after major knee surgery compared with morphine
analgesia, while capsule and synovial membrane cytokines
(IL6, TNF, IL1, IL10) and plasma cytokine concentrations
(IL6, IL1b, TNF, IL10, sTNF-R1) did not differ between the
study groups.
Freise and colleagues20 26 showed that liver perfusion and
hepatic inflammatory response might be influenced by thoracic epidural anaesthesia independently from cardiac output.
These animal studies demonstrate that thoracic epidural
anaesthesia can cause effective sympathetic block with subsequent reductions in inflammation. The effects of thoracic
epidural anaesthesia on C-reactive protein levels in patients
undergoing cardiac bypass surgery have been investigated
by Palomero and colleagues.27 Despite an attenuated inflammatory response in those cases with epidural anaesthesia,
this effect was not reflected by improved outcome variables.

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variables are improved by epidural analgesia in comparison

with conventional opioid-based analgesia concepts. The
largest available meta-analysis was published in 2000 by
Rodgers and colleagues10 and included data available before
January 1997. Although the analysis is impressive, there are
some weaknesses based on current standards. First, the
analysis included patients undergoing various neuraxial techniques, including spinal, epidural, or epidural anaesthesia,
combined with general anaesthesia in comparison with
general anaesthesia alone. Such significant clinical heterogeneity limits meta-analysis. Thus, the data by Rodgers and colleagues are appropriate for a systematic review but not for
meta-analysis. Secondly, many of the included studies were
rather small, with ,100 patients. Thirdly, the oldest studies
were published in 1971 and many in the 1980s. The progress
in anaesthesiology and surgery since that time has been enormous. Therefore, these data simply do not reflect todays
practice. Fourthly, many of the included studies have methodological weaknesses, such as not using allocation concealment11 or incomplete reporting of outcome data.12 In the
light of these issues, the main conclusion of Rodgers analysis
that neuraxial anaesthesia reduces mortality compared with
general anaesthesia is questionable.
Newer, more conservative meta-analyses have drawn less
optimistic conclusions. Two Cochrane analyses showed
benefits of epidural analgesia for major abdominal
surgery13 and abdominal aortic surgery.14 The clearest
finding in that light is that epidural analgesia provides
superior analgesia compared with opioid-based analgesia.
The use of epidural analgesia resulted in reduced need for
postoperative mechanical ventilation, reduced rate of postoperative myocardial infarction, and reduced gastric and
renal complications. However, these benefits did not result
in a reduction in mortality.
Owing to the need for anticoagulation and the consecutive risk of epidural haematoma, thoracic epidural analgesia
for open heart surgery is even more controversial than epidural analgesia for major abdominal surgery. A recent
meta-analysis tried to answer the question of potential
risks and benefits of thoracic epidural anaesthesia for heart
surgery.15 Once again the authors showed some benefits,
such as a reduction of respiratory complications and supraventricular arrhythmias. There was no evidence for a
reduction in myocardial infarction, stroke, or mortality.

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Kettner et al.

Table 1 Recent studies investigating the influence of regional anaesthesia on various outcome parameters
Study

Regional anaesthetic technique

Study topic

Anti-inflammatory effects
Martin and colleagues25

Combined sciatic and femoral nerve blockade

Knee surgery and inflammation

Freise and colleagues26

Thoracic epidural anaesthesia

Liver perfusion and hepatic inflammatory

response

Palomero and colleagues27

Thoracic epidural anaesthesia

Cardiac bypass surgery and C-reactive

protein levels

Martin and colleagues25

Combined sciatic and femoral nerve blockade

Improved function after major knee

surgery

Capdevila and colleagues28

Epidural anaesthesia, peripheral nerve blockade

Improved function after major knee

surgery

Shuang and colleagues29

Thoracic epidural anaesthesia

Bridging for surgery during cardiac failure

van Lier and colleagues30

Thoracic epidural anaesthesia

Chronic obstructive disease and major

abdominal surgery

Powell and colleagues31

Thoracic paravertebral blockade

Less post-pneumectomy complications as

compared with thoracic epidural
anaesthesia

Thoracic epidural anaesthesia

Improved bowel function

Naesh and colleagues37 38

Lumbar epidural anaesthesia

Positive influence on platelet aggregation

Delis and colleagues39

Epidural anaesthesia

Prevention of perioperative venous stasis

Davies and colleagues40

Systemic administration of local anaesthetic

Direct effect on platelet function

Exadaktylos and colleagues44

Thoracic paravertebral blockade

Positive effect on breast cancer outcome

(retrospective analysis)

Biki and colleagues46

Epidural anaesthesia

Positive effect on prostate cancer outcome

(retrospective analysis)

Myles and colleagues47

Epidural anaesthesia

No improved outcome after major

abdominal cancer surgery

Functional recovery

Cardiopulmonary effects

Taqi and colleagues34

Effects on blood coagulation

Cancer recurrence

Functional recovery
25

A study by Martin and colleagues investigating pain at rest

and upon movement after major knee surgery observed
improved knee flection in the immediate postoperative
period and 1 month after surgery with regional anaesthesia
compared with systemic opioid pain control. These results
are supported by a study from Capdevila and colleagues,28
where immediate and long-term postoperative knee movement was significantly better with epidural and peripheral
nerve block compared with systemic pain therapy. Whether
bolus or continuous administration via perineural or epidural
catheters provide better results during the postoperative
period remains unanswered.

Cardiopulmonary effects
The cardiac and pulmonary effects of neuraxial regional
anaesthesia are well known. Whereas direct cardiac and pulmonary effects of peripheral nerve block are negligible, neuraxial anaesthesia causes profound sympathetic block with
subsequent consequences on cardiac output and peripheral
perfusion. Cardiopulmonary effects of neuraxial block are

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well investigated, and thoracic epidural anaesthesia can be

used even during cardiac failure as a bridge to surgery.29
According to a meta-analysis by Svircevic and colleagues,15
epidural anaesthesia during cardiac surgery reduces postoperative supraventricular arrhythmias and respiratory complications, but definitive conclusions regarding mortality,
myocardial infarction, and stroke were precluded due to the
diversity of data, although a reduced risk of cardiopulmonary
complications was estimated.
van Lier and colleagues30 investigated the impact of epidural anaesthesia in patients with chronic obstructive pulmonary disease on outcome after major abdominal surgery
in 324 patients. Postoperative pulmonary complications
were reduced mainly in patients with severe chronic obstructive pulmonary disease. Powell and colleagues31 compared
the influence of paravertebral block with thoracic epidural
block on major post-pneumonectomy complications in 312
patients. Although some data favour paravertebral block
regarding the incidence of postoperative complications in
this patient population, further data are required for definitive statements regarding the optimal regional anaesthetic
method during lung surgery.

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Gastrointestinal effects

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Regional anaesthesia and outcome

It is likely that reduction or even avoidance of opioids and

optimized postoperative pain therapy via neuraxial regional
analgesia is superior regarding pulmonary postoperative
function. However, the use of neuraxial regional anaesthesia
for major surgery should be carefully balanced. Individual
risk assessment and physician skills are important to attain
optimal regional anaesthesia effects during abdominal and
thoracic surgery.

Gastrointestinal effects
Postoperative ileus is an important morbidity and mortality
factor. Thoracic epidural anaesthesia causes sympatholysis
and improved microcirculation with subsequent improved
bowel function.32 34 The preventions and treatment of postoperative ileus are multifactorial and should include the
avoidance of opioids, use of epidural block, use of a nasogastric tube, and correction of electrolyte imbalance.32

The effects of neuraxial regional anaesthesia on platelet

function are well known.35 38 Recent publications show
that epidural anaesthesia also prevents perioperative
venous stasis.39 The incidence of perioperative venous
thrombosis can be significantly reduced, as shown by a
Cochrane meta-analysis from Parker and colleagues.16
With regard to the influence of various regional anaesthetic techniques on blood coagulation, local anaesthetics
do have a direct effect on platelet function.40 42 Thus, a
combination of indirect and direct mechanisms for regional
anaesthesia effects on blood coagulation seems to be
responsible for the antithrombotic effects of regional block.

Cancer recurrence
Studies both in vivo and in vitro suggest several mechanisms
by which cancer surgery might affect cellular immunity:
stress response to tissue injury, general anaesthesia, and
the use of perioperative opioids. A hypothesis currently
under investigation is that regional anaesthesia can influence cancer recurrence by several mechanisms: decreased
neuroendocrine stress response to surgical tissue injury,
reduced need for general anaesthesia, and reduced opioid
consumption.43 In addition, pain is an important stress
factor and perioperative pain therapy is superior when successful regional anaesthesia is performed.
The relationship between regional anaesthesia and cancer
recurrence is one of the most fascinating topics in anaesthesia today. The concept that anaesthesia can influence the
outcome of cancer would raise our speciality to a new
level. An initial retrospective analysis of survival rates after
breast cancer surgery showed impressively improved results
for patients treated with paravertebral block (94%
metastasis-free and survival) compared with those receiving
general anaesthesia (77% metastasis-free and survival).44 A
prospective multicentre trial will determine whether these
retrospective data can be confirmed.45

Regional anaesthesia and outcome: what

we know and what we wish
Whether regional anaesthesia influences outcome after
surgery is a controversial topic. Several meta-analyses have
investigated this important topic with controversial results.
Cochrane analyses probably represent the highest standards
of meta-analyses. Accordingly, conclusions are very carefully
expressed by authors of Cochrane reviews. On the other
hand, large outcome studies and meta-analyses are only
one side of the coin. Expert opinions represent lower levels
of evidence that are still useful in informing current practice,
but must be considered even more cautiously. In skilled
hands, various regional anaesthetic techniques are powerful
tools providing almost perfect perioperative pain therapy.
Using an optimal balance between appropriate techniques,
application of advanced equipment, and optimal doses of
drugs, regional anaesthesia plays an important role in perioperative medicine. No outcome study or meta-analysis considers the individual skills and the directly associated success
rates. In the authors opinion, failed blocks are probably the
most important factors for negative outcome. Improvement
in outcome can probably be achieved when the skills of individual practitioners are improved and regional anaesthesia is
used wisely and appropriately leading to reduced failure
rates.
Whether specific regional anaesthetic techniques or local
anaesthetics influence the course of illness is an important
topic in the future. The theoretical approach is fascinating,
and retrospective data in specific fields are promising.
Either way, performing a successful regional block during
cancer surgery is rarely harmful and should therefore be performed whenever applicable. Whether it influences cancer
outcomelets find out!

Conflict of interest
None declared.

Funding
Supported solely by departmental funds.

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Effects on blood coagulation

A positive influence of regional anaesthesia on

cancer outcome after surgery is also suggested for prostate cancer.46 On the other hand, Myles and colleagues47
did not find a positive correlation between the use of epidural anaesthesia and abdominal cancer surgery. Therefore, the entire topic of regional anaesthesia and cancer
is evolving and potentially complex. Further experimental
and prospective clinical studies have to investigate possible
beneficial effects of regional anaesthesia on cancer
recurrence.

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