Meta-Analysis of Thoracic Epidural Anesthesia Versus General Anesthesia For Cardiac Surgery

Meta-analysis of Thoracic Epidural Anesthesia versus
General Anesthesia for Cardiac Surgery

Vesna Svircevic, M.D.,* Diederik van Dijk, M.D., Ph.D., Arno P. Nierich, M.D., Ph.D.,
Martijn P. Passier, M.D., Cor J. Kalkman, M.D., Ph.D., Geert J.M.G. van der Heijden, Ph.D.,#
Leon Bax, Ph.D.**
ABSTRACT
What We Already Know about This Topic

Whether the addition of thoracic epidural anesthesia to general anesthesia provides an overall benefit to patients undergoing cardiac surgery is controversial
Background: A combination of general anesthesia (GA)

with thoracic epidural anesthesia (TEA) may have a beneficial effect on clinical outcomes after cardiac surgery. We have
performed a meta-analysis to compare mortality and cardiac,
respiratory, and neurologic complications in patients undergoing cardiac surgery with GA alone or a combination of GA
with TEA.
Methods: Randomized studies comparing outcomes in patients undergoing cardiac surgery with either GA alone or
GA in combination with TEA were retrieved from PubMed,
Science Citation index, EMBASE, CINHAL, and Central
Cochrane Controlled Trial Register databases.
Results: The search strategy yielded 1,390 studies; 28 studies that included 2,731 patients met the selection criteria.
Compared with GA alone, the combined risk ratio for patients receiving GA with TEA was 0.81 (95% CI: 0.40
1.64) for mortality, 0.80 (95% CI: 0.521.24) for myocardial infarction, and 0.59 (95% CI: 0.24 1.46) for stroke.
The risk ratios for the respiratory complications and su-
What This Article Tells Us That Is New

In a meta-analysis of more than 2,700 cardiac surgery patients
in 28 studies, the addition of thoracic epidural anesthesia significantly reduced supraventricular arrhythmias and respiratory complications, but not mortality, myocardial infarction, or
stroke
Because epidural hematoma did not occur in these small
studies, overall benefit to harm could not be calculated
praventricular arrhythmias were 0.53 (95% CI: 0.40 0.69)

and 0.68 (95% CI: 0.50 0.93), respectively.
Conclusions: This meta-analysis showed that the use of
TEA in patients undergoing cardiac surgery reduces the risk
of postoperative supraventricular arrhythmias and respiratory complications. The sparsity of events precludes conclusions about mortality, myocardial infarction, and stroke, but
the estimates suggest a reduced risk after TEA. The risk of
side effects of TEA, including epidural hematoma, could not
be assessed with the current dataset, and therefore TEA
should be used with caution until its benefit-harm profile is
further elucidated.
* Anesthesiology Resident, Department of Anesthesiology, University Medical Center Utrecht, Utrecht, The Netherlands; Anesthesiologist, Departments of Anesthesiology and Intensive Care,
University Medical Center Utrecht; Anesthesiologist, Department
of Thoracic Anesthesiology, Isala Clinics, Zwolle, The Netherlands;
Anesthesiologist, Department of Anesthesiology, Alysis Rijnstate
Hospital, Arnhem, The Netherlands; Professor of Anesthesiology,
Department of Anesthesiology, University Medical Center Utrecht;
# Associate Professor, Julius Center for Health Sciences and Primary
Care, University Medical Center Utrecht; ** Associate Professor,
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, and Kitasato Clinical Research Center, Kitasato
University, Sagamihara, Japan.
Received from the Division of Perioperative Care and Emergency Medicine, Department of Anesthesiology, University Medical
Center Utrecht, Utrecht, The Netherlands. Submitted for publication
July 6, 2010. Accepted for publication September 1, 2010. Support
was provided solely from institutional and/or departmental sources.
Address correspondence to Dr. Svircevic: Division of Perioperative Care and Emergency Medicine, Department of Anesthesiology, University Medical Centre Utrecht, Mailstop Q 04.2.313,
P.O. Box 85500, 3508 GA Utrecht, The Netherlands. v.svircevic@
umcutrecht.nl. Information on purchasing reprints may be found
at www.anesthesiology.org or on the masthead page at the beginning of this issue. ANESTHESIOLOGYs articles are made freely
accessible to all readers, for personal use only, 6 months from the
cover date of the issue.
UTCOMES after cardiac surgery have been markedly

improved over recent decades because of advances in
anesthesiology, surgery, cardiopulmonary bypass, and postoperative care.1,2 A combination of general anesthesia (GA)
with thoracic epidural anesthesia (TEA) may have an additional beneficial effect on outcomes after cardiac surgery,35
compared with GA alone. TEA may enhance coronary perfusion, improve myocardial oxygen balance, and reduce the
incidence of tachyarrhythmias and perioperative myocardial
ischemia through sympathycolysis.6,7 The excellent analgesia
This article is accompanied by an Editorial View. Please see:
Royse CF: Epidurals for cardiac surgery: Can we substantially
reduce surgical morbidity or should we focus on quality of
recovery? Anesthesiology 2011; 114:2323.
Copyright 2011, the American Society of Anesthesiologists, Inc. Lippincott

Williams & Wilkins. Anesthesiology 2011; 114: 271 82
Anesthesiology, V 114 No 2
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February 2011
Thoracic Epidural Anesthesia for Cardiac Surgery
adjudication of study endpoints; and completeness of (follow-up) data. The decision on the suitability of a study for
our analysis was compared by two authors (V. S. and
M. P. P.). Discrepancies were resolved by discussion, where
necessary, with the help of a third reviewer (D. v. D.).
that is associated with TEA facilitates early tracheal extubation and may prevent respiratory complications.8,9
TEA in cardiac surgery is controversial, considering possible complications of TEA, including spinal cord compression caused by a hematoma or abscess. Systematic anticoagulation needed during cardiopulmonary bypass could
increase the incidence of epidural hematoma related to the
use of an epidural catheter.10 More commonly, the intense
sympathycolysis may lead to systemic hypotension, which
can be difficult to correct. The majority of studies comparing
GA with the combination of GA and TEA were insufficiently
powered to quantify the effect of TEA on clinical outcome
measures. A previous meta-analysis by Liu et al.11 was published in 2004 and included 1,178 patients. This meta-analysis found no difference in rates of mortality or myocardial
infarction after cardiac surgery for patients receiving TEA
versus GA alone. Since then, several new randomized studies
evaluating TEA in cardiac surgery have been published.
The purpose of this study was to update the meta-analysis
and explore reasons for discrepancies between the clinical
trials that have evaluated the effects of TEA on mortality and
cardiac, respiratory, or neurologic complications in patients
undergoing cardiac surgery.
Data Extraction and Principal Endpoints

Data were extracted from the full-text article of each included
study, using a standardized data-extraction form (appendix
2). The principal endpoints for the current analysis were
mortality, acute myocardial infarction, supraventricular
tachyarrhythmia, and respiratory or neurologic complications (e.g., stroke, epidural hematoma, or abscess). These
endpoints were chosen because of their clinical importance
and frequency of reporting. More recent studies have also
assessed the lengths of stay in the intensive care unit and in
the hospital, but not enough data were available to pool a
reliable estimate. From all included studies, data on the number of events for the endpoints were extracted for both the
TEA and the GA groups. Because the endpoints were analyzed separately, it is possible that studies attributed information to one, two, or more endpoints. The definition of myocardial infarction and stroke were those used in each study,
although a sensitivity analysis was performed with an endpoint combining the two. The endpoint respiratory complication was defined as respiratory insufficiency requiring reintubation, prolonged ventilation, or a ventilatory-associated
pneumonia, according to the reported data in the studies.
Materials and Methods

Search Process
We combined various synonyms for cardiac surgical procedures and epidural anesthesia to retrieve studies comparing
GA and TEA from CENTRAL, PubMed, EMBASE,
CINAHL, and Web of Science (SCI/SSCI). For EMBASE
and PubMed, we combined our topical search filter with a
sensitive evidence-based search query for effectiveness studies. Bibliographies and references of selected publications
and systematic reviews and editorials on cardiac surgery and
epidural anesthesia were screened using Web of Science
(SCI/SSCI).7,8,11 The complete search strategy is presented
in appendix 1. The current study only used published literature data, and no institutional review board approval was
required by our institute.
Only randomized clinical studies published before January 1, 2010, that included adult patients (i.e., 18 yr or older)
undergoing cardiac surgery, comparing the outcomes of the
patients undergoing cardiac surgery with GA or the combination of GA and TEA, were considered for inclusion in the
review. We applied no restrictions with respect to language.
Statistical Methods
Meta-analysis was performed with MIX 2.0 Pro (release
2.0.0.9; BiostatXL, Tokyo, Japan) and Stata (release 10.0;
StataCorp., College Station, TX). Patients who only had GA
were treated as control groups, and patients with TEA were
treated as intervention groups. For each trial, we calculated
the risk per treatment group by dividing the number of
events by the number of patients randomized. Subsequently,
risk ratio (RR) and the corresponding 95% CIs were calculated for each trial, where a risk ratio less than 1 indicates an
effect in favor of TEA. For trials without events in the control
group, the RR and its SE could not be calculated. To deal
with this problem, it is common to add 0.5 or a smaller value
to each cell in the contingency table of these trials. This is,
nevertheless, known to cause bias13 when treatment arm sizes
are unequal, as was the case with a number of the included
studies. We therefore used a treatment arm dependent approach, in which the correction was proportional to the size
of the relevant treatment arm.14 Sensitivity analyses were
planned to assess the impact of different continuity corrections and weighting methods. To provide readers with information about control (baseline) risks and experimental
group risks, LAbbe plots were created for each outcome.
The presence of heterogeneity of outcomes across trials
was assessed using the I2 measure and the DerSimonian
Laird two-step between-study variance estimate, t2.15 The
Risk of Bias Assessment

All publications found during the search were manually and
independently reviewed by the same two authors (V. S. and
M. P. P.), using the risk of bias assessment tool12 (appendix
2). Criteria that were used for assessing the risk of bias of the
included studies were: method of randomization; concealed
treatment allocation; blinding during pre-, peri-, and postoperative care; blinded data collection and analysis; blinded
Anesthesiology 2011; 114:271 82
272
Svircevic et al.
PERIOPERATIVE MEDICINE
heterogeneity was small (I2: 0% [95% CI: 0 57%]; t2

0). Combining the data from 13 studies yielded a fixedeffect estimate of the RR of 0.81 (95% CI: 0.40 1.64).
Results of the primary meta-analysis for mortality are presented in table 2 and figure 2. Different continuity corrections and weighting methods had little effect on the
results and yielded in RRs ranging from 0.79 to 0.81.
Using mortality and myocardial infarction as combined
outcome (assuming independence of the events) led to an
RR of 0.79 (95% CI: 0.54 1.16).
Myocardial Infarction
Fifteen studies with 2,041 patients reported on myocardial
infarction. Of the 15 studies, two studies reported no events
in both the TEA and the GA arms and they were excluded
from the primary analysis. The analysis dataset contained
1,849 patients with 33 events in the TEA arm and 43 events
in the GA arm. The I2 statistic (I2: 0%; 95% CI: 0 57%), as
well as the t2 statistic (t2: 0), indicated that the statistical
heterogeneity was low. Synthesis of the 13 studies showed
no evidence for a difference in the risk of acute myocardial
infarction between groups of patients receiving TEA,
compared with patients receiving GA alone (RR: 0.80;
95% CI: 0.521.24; see table 2 and fig. 3). Sensitivity
analyses with different continuity corrections and weighting methods had little effect on the results, with RRs
ranging from 0.79 to 0.81.
Fig. 1. Flowchart of the database search and selection

process.
dataset was graphically explored by forest, Galbraith,

LAbbe, and funnel plots. We intended to use random-effects
models, while anticipating that they effectively become
fixed-effect syntheses when the between-study variance t2 is
estimated as being 0. The MantelHaenszel method was
used for the fixed-effect syntheses.
Although a complete synthesis of the dataset was planned,
it was anticipated that time to extubation as well as other
factors that vary over time could be varying between studies
and causing heterogeneity in the estimates. A metaregression
as well as subgroup analyses based on year of publication and
time to extubation were therefore planned a priori. In addition, the presence of small study effects, indicative of biases
related to selective reporting and selective publication of
studies, was assessed with plots and Peters regression test.16
Supraventricular Tachyarrhythmias
Fourteen studies with 2,194 patients reported on supraventricular tachyarrhythmias, with 300 events in the TEA and
410 events in the GA arms. There were no studies without
events. Heterogeneity was substantial (I2: 62% [95% CI:
3379%]; t2 0.21), and we applied a random-effects
model for the synthesis. The resulting RR was 0.68 (95% CI:
0.50 0.93), showing that combining TEA with GA may be
associated with a lower risk of supraventricular tachyarrhythmias than the use of GA alone. The 95% prediction interval
ranges from 0.25 to 1.83. Meta-analysis results are shown in
table 2 and figure 4.
Results
Results of our search strategy are shown in figure 1. We have
identified 1,390 titles, of which 1,167 studies did not satisfy
the selection criteria or were duplicate publications retrieved
from the five different databases. Full review was performed
on 223 studies, of which 28 publications met all inclusion
criteria. These 28 publications reported on a total of 2,731
patients: 1,416 patients with GA and 1,315 patients with GA
plus TEA. Characteristics of the included trials are presented
in table 1.
Respiratory Complications
A total of 13 studies with 1,886 patients presented data on
the number of patients who had had respiratory complications. The respiratory complications were rare, with five
studies reporting no events in one of the treatment arms and
one study reporting no events at all. The primary synthesis
was performed on the 12 studies that had one or more events
in the study. There were 67 events in the TEA and 128 events
in the GA arms. The I2 statistic was low (I2: 0%; 95% CI:
0 57%), and the t2 statistic also showed no evidence of
statistical heterogeneity (t2: 0). Combined fixed-effect analysis of data from 1,858 patients of 12 studies showed a lower
risk of respiratory complications for patients receiving TEA
and GA during surgery, compared with those receiving GA
Mortality
All 28 studies reported mortality. None of the studies showed
significant reduction in risk with TEA. The reported events
were extremely sparse, with 25 studies reporting no events in
either the TEA or the GA arms and 15 studies reporting no
events at all. A total of 9 events were reported in the TEA
arm, compared with 13 events in the GA arm. In the primary
analysis, the 15 studies that did not report any events were
excluded, resulting in 13 studies with a total number of
1,906 patients contributing to the dataset. The statistical
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Svircevic et al.
Table 1. Characteristics of the Studies Contributing Data to this Meta-analysis

Participants
Year of
Publication
TEA
GA
GA
Concealed
Allocation
Blinding
Lost to
Follow-up (n)
Rein
Liem31
1987
1989
1992
30
8
27
30
8
27
Kirno20
Stenseth32
Moore34
Stenseth9
Brix-Christensen35
1994
1994
1995
1996
1998
10
18
9
26
10
10
9
26
Loick36
1999
25
25
Tenling37
1999
14
Scott6
Bach38
Fillinger39
2001
2002
2002
Priestley5
Author
Reported Outcome Measures
Interventions (Epidural Medication)
0
4
Mortality
Respiratory complications
Neurologic complications
Mortality
Mortality
Morphine
?
?
Myocardial infarction
Supraventricular tachycardias
Mortality
Mortality
Mortality
Mortality
Mortality
14
Mortality
206
13
30
206
13
30
12
0
0
Mortality
Mortality
Mortality
2002
50
50
Mortality
Vries40
2002
30
30
Mortality
Berendes41
2003
36
36
Mortality
Royse17
2003
37
37
Mortality
Kendall42
2004
Mortality
Nygard6
2004
79
79
Mortality
El Baz
29
30
Mortality
274
Bupivacaine (bolus plus infusion)

Bupivacaine/sufentanil (bolus plus
infusion)
Mepivacaine
(Bolus)

Bupivacaine
(Bolus plus infusion)
infusion)
infusion)

infusion)

Bupivacaine/morphine (bolus plus
infusion)
Ropivacaine/fentanyl (bolus plus

infusion)
Bupivacaine.sufentanil (bolus plus

infusion)
Bupivacaine.sufentanil (bolus plus

infusion)

infusion)
Bupivacaine/fentanyl (bolus plus

infusion)

infusion)
(continued)
Svircevic et al.
Table 1. Continued
Participants
Author
Year of
Publication
TEA
GA
GA
Concealed
Allocation
Blinding
Lost to
Follow-up (n)
Reported Outcome Measures
Barrington43
Lundstrom44
2005
2005
60
26
60
26
Mortality
Mortality
Hansdottir20
2006
58
58
16
Mortality
Kilickan18
Langunilla45
2006
2006
40
25
40
25
Mortality
Mortality
Bakhtiary46
2007
66
66
Heijmans47
2007
15
15
Mortality
Caputo48
Svircevic49
Total
2009
2010
36
325
1,315
38
329
1,416
Mortality
Mortality
Interventions (Epidural
Medication)
Ropivacaine/fentanyl (boluses)

infusion)
Bupivacaine/fentanyl (bolus plus

infusion)

infusion)
Ropivacaine.sufentanil (bolus plus
infusion)

infusion)
Bupivacaine/morphine
Mortality
GA general anesthesia; TEA thoracic epidural anesthesia.
alone (RR: 0.53; 95% CI: 0.40 0.69). Alternative continuity corrections and weighting models yielded RRs of 0.52
0.55.
rate, seven studies reported no events at all, and only six

studies with 1,469 patients were used for the primary analysis. There were 6 events in the TEA and 11 events in the GA
arms. There was no evidence of statistical heterogeneity (I2:
0%; 95% CI: 0 75%). Formal synthesis yielded an RR of
0.59 (95% CI: 0.24 1.46), indicating that the use of TEA
was associated with a lower risk of stroke that may be substantial. However, the risk ratio estimate was not statistically
Neurologic Complications
None of the trials reported events of epidural hematoma or
abscess. Thirteen trials with 1,986 patients reported on
stroke events. However, because of the extremely low event
Table 2. Effect of TEA versus GA on Mortality, Myocardial Infarction, Supraventricular Tachyarrhythmia, Respiratory
Complications, and Stroke
Events
Outcome
Studies
RR
Mortality
Supraventricular tachyarrhythmias
Stroke
28
13
14
12
6
0.81
0.80
0.68
0.53
0.59
95% CI
0.40
0.52
0.50
0.40
0.24
1.64
1.24
0.93
0.69
1.46
Patients
TEA
GA
TEA
GA
9
33
300
67
6
13
43
410
128
11
931
899
1,069
915
735
975
950
1,125
943
734
A risk ratio of 1.00 indicates an increased risk in the TEA group.

GA general anesthesia; RR risk ratio; TEA thoracic epidural anesthesia.
275
Svircevic et al.
Fig. 2. Risk ratios and forest plot for mortality in the first 2 weeks after surgery. GA general anesthesia; RR risk ratio; TEA
thoracic epidural anesthesia.
Discussion
significant and was based on a small number of events. Alternative weighting models had little impact on the results,
but alternative continuity corrections that integrated the excluded studies yielded RRs from 0.52 to 0.77.
We have conducted a meta-analysis of clinical trials comparing the effects of cardiac surgery with and without TEA on
mortality and cardiac, respiratory, and neurologic complications. Our meta-analysis showed statistically significant reductions in the incidence of supraventricular tachyarrhythmias and respiratory complications after TEA. There were no
significant differences in the incidences of mortality, myocardial infarction, and stroke.
The potential of TEA for decreasing tachyarrhythmias
has been reported before3,17,18 and was confirmed in this
meta-analysis. However, the included studies were heterogeneous, and the confidence intervals around the risk ratio
estimates were wide. The study by Scott et al.3 in 420 patients
was contributing the most to this result. In this study,
Additional Evaluations
Metaregression did not show likely associations between the
study outcome and factors varying over the years of execution
of the individual studies or risk of bias items for any of the
outcomes. Neither graphical explorations nor formal regression tests showed evidence of small study effects due to selective dissemination of studies or study results for any of the
above-mentioned endpoints. Figure 5 contains risk-based
LAbbe plots, showing the per-study control group (baseline)
risks, index group risks, and their relationship for all endpoints in a single graph.
Fig. 3. Risk ratios and forest plot for supraventricular tachyarrhythmias in the first 2 weeks after surgery. GA general
anesthesia; RR risk ratio; TEA thoracic epidural anesthesia.
276
Svircevic et al.
Fig. 4. Risk ratios and forest plot for respiratory complications in the first 2 weeks after surgery. GA general anesthesia; RR
risk ratio; TEA thoracic epidural anesthesia.
-blockers were discontinued 5 days perioperatively. Moreover, the patients randomized to TEA received the cardioprotective drug, clonidine, through their epidural catheter.
This cardioprotective drug19 was not administered to the
control patients. The withdrawal of -blockers in all study
patients and the selective use of clonidine in the patients
randomized to TEA may explain the large benefit of TEA on

supraventricular arrhythmias found in this trial. Although
the Scott study was encouraging, most studies published
since then were unable to repeat its results. A recent, welldesigned study by Hansdottir20 revealed no benefits of TEA
on the incidence of tachyarrhythmias, plus a 17% failure of
epidural catheter insertion. Recent studies showed that postoperative supraventricular tachyarrhythmias can also be reduced with less invasive treatments, such as -blockers and
amiodarone.6,21,22 The majority of the studies included in
this meta-analysis did not report whether the patients also
used drugs to prevent postoperative arrhythmias. It is therefore unclear whether TEA has an additional preventive effect
in patients who are also administered prophylactic antiarrhythmic drugs after their operation.
Our meta-analysis also showed that TEA results in a statistically significant reduction in postoperative respiratory
complications, which is consistent with previous meta-analyses.8,11 This may be explained by the superior analgesia after
TEA, which facilitates earlier spontaneous respiration in the
intensive care unit and faster tracheal extubation. It has been
shown, however, that other strategies that allow earlier tracheal extubation can also reduce respiratory complications.2325 A previous meta-analysis by Liu11 showed that
pulmonary complications after cardiac surgery can also be
reduced with spinal anesthesia. Interestingly, this benefit was
not explained by a shorter time to extubation. As the risk of
an epidural hematoma is considerably lower after a single
spinal injection than after insertion of an epidural catheter,
spinal anesthesia might be a viable option for cardiac surgical
patients with a high risk of pulmonary complications.
There are several limitations associated with the included
randomized studies that warrant caution in the interpretation of the results of this meta-analysis. First, the time period
in which the studies were undertaken spanned 30 yr. The
Fig. 5. Risk-based LAbbe plots for baseline, index group

risks, and relationship for endpoints. GA general anesthesia; MI myocardial infarction; RC respiratory complications; SVT supraventricular tachyarrhythmias; TEA thoracic epidural anesthesia.
277
Svircevic et al.
quality of anesthesiological and intensive care has clearly improved over these years. It is possible that some beneficial
effects of TEA, such as earlier extubation, are currently also
achieved with modern general anesthetics. Second, most of
the included studies were designed to evaluate the effect of
TEA on intermediate or surrogate outcome measures, instead of clinical endpoints. Third, the nonstandardized coverage of clinical outcomes in most studies carries a high risk
of observer bias, in particular when the endpoint adjudication was not blinded.
Our findings are largely comparable with those of the two
previous meta-analyses.8,11 Because we were able to include
28 studies including 2,731 patients, which is substantially
more patients than in the two previous meta-analyses, the
effect estimates are more precise with narrower confidence
intervals. Although the number of patients in the current
meta-analysis is more than twice the number of patients in
previous meta-analyses, the events were extremely sparse, and
the current meta-analysis is still not sufficiently powered to
detect small beneficial or harmful effects of TEA on mortality, myocardial infarction, paraplegia, and stroke. To demonstrate statistical significance for the reduction in the incidence of myocardial infarction from 3.8% after GA to 2.8%
after TEA (as found in this meta-analysis), a sample size of at
least 10,000 patients is required. It is obvious that such a
large trial would be extremely difficult to perform.
Despite the benefit of TEA on supraventricular tachyarrhythmias and respiratory complications, our findings must
be viewed with caution. Thoracic epidural anesthesia in cardiac surgery remains controversial in the absence of a sufficiently large, statistically significant effect on mortality,
stroke, or myocardial infarction while possible hazardous
complications of TEA, such as epidural hematoma or abscess, must be taken into account. Systematic anticoagulation needed during cardiopulmonary bypass could increase
the incidence of epidural hematoma related to the use of an
epidural catheter.10 More commonly, the intense sympathycolysis may lead to systemic hypotension, which can be difficult to correct.
In the included studies, no cases of epidural hematoma
were reported, but this devastating complication is too rare to
evaluate in randomized studies. There are a few reports26,27
on neuraxial hematoma in cardiac surgery, of which some
have directly been linked to TEA.28 The benefit-harm tradeoff could not be explored in the current framework of metaanalysis of randomized trials. However, given the severity of
this complication and the lack of a clear beneficial effect on
mortality, stroke, or myocardial infarction, the potential
benefits of TEA in cardiac surgery may not be worth the
potential risks.
In conclusion, this meta-analysis showed that the use of
TEA in patients undergoing cardiac surgery reduces the risk
of postoperative supraventricular arrhythmias and respiratory complications. The sparsity of events precludes conclusions about mortality, myocardial infarction, and stroke, but
the estimates suggest a reduced risk after TEA. The risk of

side effects of TEA, including epidural hematoma, could not
be assessed with the current dataset, and therefore TEA
should be used with caution until its benefit-harm profile is
further elucidated.
Appendix 1. Search Strategy

Database
PubMed and MEDLINE (1966 2010)
Searchfilter
((Cardiac Surgical Procedures[MeSH] or cardiac surgery[tiab] or
heart surgery[tiab] or cardiac surgical procedures[tiab] or cardiopulmonary bypass[tiab] or cardiothoracic*[tiab] or CABG[tiab]) not
Pulmonary Surgical Procedures[MeSH]) and (Analgesia, Epidural[MeSH] or Anesthesia, Epidural[MeSH] or Anesthesia,
Spinal[MeSH] or epidural*[tiab] or peridural*[tiab] or
extradural*[tiab] or spinal*[tiab] or subarachnoid*[tiab] or
intrathecal*[tiab] or neuraxial*[tiab]) and ((randomized controlled trial [pt] or controlled clinical trial [pt] or randomized
controlled trials [mh] or double-blind method [mh] or singleblind method [mh] or clinical trial [pt] or clinical trials [mh]
or (clinical trial [tw])) or ((singl* [tw] or doubl* [tw] or
trebl* [tw] or tripl* [tw]) and (mask* [tw] or blind* [tw])) or
(placebos [mh] or placebo* [tw] or random* [tw] or research
design [mh:noexp] or comparative study [mh] or evaluation
studies [mh] or follow-up studies [mh] or prospective studies
[mh] or control* [tw] or prospective* [tw] or volunteer* [tw]
not (animals [mh] not human [mh])))
Database
Science Citation Index Expended and Social Sciences Citation Index (1988 2010)
Searchfilter
1988 2004/07TI ((epidural* or peridural* or extradural*
or spinal* or subarachnoid* or intrathecal* or neuraxial*) and
(anesthes* or anaesthes* or analges*) and (card* surg* or
heart surg* or CABG or coronar* arter* bypass* or coronar*
bypass* or heart* valv* surg*) and (metaanalysis or metaanalysis or review or consensus or guideline or random* or
trial* or control* or ((singl* or doubl* or trebl* or tripl*) and
(blind* OR mask*))))
Database
EMBASE (1989 2010)
Searchfilter
(((heart-surgery in su) or (cardiopulmonary-bypass in su))
or ((coronary artery bypass surgery or coronary artery surgery or
coronary bypass graft surgery or coronary artery bypass graft or
coronary bypass graft or coronary artery bypass graft* or coronary bypass graft* or CABG or ((off pump or offpump or offpump) and (coronary surgery)) or open heart surgery or heart
278
Svircevic et al.
surgery or heart valve surgery or cardiopulmonary bypass) and

((xrec ab) or (xrec ti)))) and (((epidural or peridural or
extradural or spinal or subarachnoid or intraspinal or intrathecal
or neuraxial) and ((xrec ab) or (xrec ti))) or ((spinal-anesthesia or intraspinal-drug-administration or epidural-anesthesia) in su)) and (((controlled study or controlled trial or clinical
study or major clinical study or clinical trial or randomized
controlled trial or random* or trial*) and ((xrec ab) or (xrec
ti))) or ((clinical study or controlled study) in su))
explode evaluation studies/all topical subheadings/all age

subheadings or prospectieve study) and ((xrec ab) or
(xrec ti)))) or (clinical-trials in de))
Database
Cochrane Anaesthesia Review Group trials register and
CENTRAL (the current issue of The Cochrane Library)
Searchfilter
1.
2.
3.
4.
5.
Database
CINAHL (19822010)
Searchfilter
(((heart-surgery in de)or(cardiopulmonary-bypass in de)) or
(((coronary artery bypass surgery or coronary artery surgery
or coronary bypass graft surgery or coronary artery bypass
graft or coronary bypass graft or coronary artery bypass graft*
or coronary bypass graft* or CABG or ((off pump or offpump or off-pump) and coronary surgery) or open heart
surgery or heart surgery or heart valve surgery or cardiopulmonary bypass)) and ((xrec ab) or (xrec ti)))) and (((epidural or peridural or extradural or spinal or subarachnoid or
intrathecal or neuraxial) and ((xrec ab) or (xrec ti))) or
(((anesthesia-spinal in de)or(injections-intraspinal in de)or(infusions-intraspinal in de)) or ((analgesia-epidural in
de)or(anesthesia-epidural in de)or(epidural-analgesia-administration in de)))) and (((clinical-trials in de) or ((Randomized controlled trial or clinical trial or explode clinical
trial/all topical subheadings/all age subheadings or (control*
or prospectiv* or volunteer*) or ((singl* or doubl* or trebl* or
tripl*) adj (blind* or mask*)) or placebo* or random* or
6.
7.
8.
9.
10.
11.
12.
ANALGESIA EPIDURAL explode all trees (MeSH)

ANESTHESIA EPIDURAL explode all trees (MeSH)
ANESTHESIA SPINAL explode all trees (MeSH)
INJECTIONS SPINAL explode all trees (MeSH)
(epidural* or peridural* or spinal* or intraspinal* or intrathecal* or neuraxial*)
(1 or 2 or 3 or 4 or 5)
CARDIAC SURGICAL PROCEDURES explode all
trees (MeSH)
CARDIOPULMONARY BYPASS explode all trees
(MeSH)
(6 and (7 or 8))
((coronary next artery next bypass next surgery) or (coronary next artery next surgery) or (coronary next bypass next
graft next surgery) or (coronary next artery next bypass next
graft) or (coronary next bypass next graft) or (coronary next
artery next bypass next graft*) or (coronary next bypass next
graft*) or cabg or (((off next pump) or offpump or offpump) and (coronary next surgery)) or (open next heart
next surgery) or (heart next surgery) or (heart next valve
next surgery) or (cardiopulmonary next bypass))
(7 or 8 or 10)
(11 and 6) 74
279
Svircevic et al.
Appendix 2. Processing-form Epidural versus Nonepidural Anesthesia in Cardiac Surgery

Article nr:
Date: //.
Name reviewer: Svircevic Passier van Dijk
First authors name
Year of publication
Study Quality
1 Group size
Neuraxial N
Control N
2 Randomized allocation Yes No Method unclear
3 Concealed allocation Yes No Method unclear
4 Number of crossovers
Neuraxial N
Control N
5 Maximum number of dropouts
Neuraxial N
Control N
6 Maximum number lost to follow-up
Neuraxial N
Control N
7 Intention to treat analyses Yes No Unclear
8 Blinded analyses Yes No Unclear
9 Blinding pre- and postsurgery care Yes No Unclear
10 Standardized pre- and postsurgery care Yes No Unclear
11 Blinding endpoints Yes No Unclear
12 Standardization endpoints Yes No Unclear
Preoperative data
13 Age
Neuraxial mean SD
Control mean SD
14 Males
Neuraxial N
Control N
15 Prior vascular surgery
Neuraxial N
Control N
16 Diabetic status: type 1 2 dialysis
Neuraxial N N N
Control N N N
17 Preoperative risk score: French score Parsonnet score Euro score
Neuraxial mean SD
Control mean SD
18 Type(s) of surgery ..
19 Type of neuraxial anesthesia: intrathecal epidural
20 Type of general anesthesia: traditional fast track 12 h fast track 6 h
21 Outcome measures
Primary endpoint
Secondary endpoints
22 Time to follow-up
23 Main Outcomes of this Study (give absolute numbers, no percentages)
Outcome
Neuraxial group
Mortality
MI
SVT
Other important outcomes:
Main conclusion(s) (see last paragraph discussion):
Remarks:
Control group
280
Svircevic et al.
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Meta-Analysis of Thoracic Epidural Anesthesia Versus General Anesthesia For Cardiac Surgery

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Meta-Analysis of Thoracic Epidural Anesthesia Versus General Anesthesia For Cardiac Surgery

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Meta-analysis of Thoracic Epidural Anesthesia versus

General Anesthesia for Cardiac Surgery

What We Already Know about This Topic

Background: A combination of general anesthesia (GA)

What This Article Tells Us That Is New

praventricular arrhythmias were 0.53 (95% CI: 0.40 0.69)

UTCOMES after cardiac surgery have been markedly

Copyright 2011, the American Society of Anesthesiologists, Inc. Lippincott

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Thoracic Epidural Anesthesia for Cardiac Surgery

Data Extraction and Principal Endpoints

Materials and Methods

Risk of Bias Assessment

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heterogeneity was small (I2: 0% [95% CI: 0 57%]; t2

Fig. 1. Flowchart of the database search and selection

dataset was graphically explored by forest, Galbraith,

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Thoracic Epidural Anesthesia for Cardiac Surgery

Table 1. Characteristics of the Studies Contributing Data to this Meta-analysis

Reported Outcome Measures

Interventions (Epidural Medication)

Anesthesiology 2011; 114:271 82

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Bupivacaine (bolus plus infusion)

Bupivacaine (bolus plus infusion)

Bupivacaine/sufentanil (bolus plus

Bupivacaine (bolus plus infusion)

Bupivacaine (bolus plus infusion)

Ropivacaine/fentanyl (bolus plus

Bupivacaine.sufentanil (bolus plus

Bupivacaine.sufentanil (bolus plus

Ropivacaine/fentanyl (bolus plus

Bupivacaine/fentanyl (bolus plus

Bupivacaine/morphine (bolus plus

Reported Outcome Measures

Bupivacaine/morphine (bolus plus

Bupivacaine/fentanyl (bolus plus

Bupivacaine (bolus plus infusion)

Ropivacaine/fentanyl (bolus plus

Bupivacaine/morphine (bolus plus

GA general anesthesia; TEA thoracic epidural anesthesia.

rate, seven studies reported no events at all, and only six

A risk ratio of 1.00 indicates an increased risk in the TEA group.

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Thoracic Epidural Anesthesia for Cardiac Surgery

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randomized to TEA may explain the large benefit of TEA on

Fig. 5. Risk-based LAbbe plots for baseline, index group

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Thoracic Epidural Anesthesia for Cardiac Surgery

the estimates suggest a reduced risk after TEA. The risk of

Appendix 1. Search Strategy

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surgery or heart valve surgery or cardiopulmonary bypass) and

explode evaluation studies/all topical subheadings/all age

Anesthesiology 2011; 114:271 82

ANALGESIA EPIDURAL explode all trees (MeSH)

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