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Regional Anesthesia

Section Editor: Terese T. Horlocker

A Comparison of Neuraxial Block Versus General


Anesthesia for Elective Total Hip Replacement:
A Meta-Analysis
William J. Mauermann, MD
Ashley M. Shilling, MD
Zhiyi Zuo, MD, PhD

BACKGROUND: A recent meta-analysis showed that compared with general anesthesia (GA), neuraxial block reduced many serious complications in patients undergoing various types of surgeries. It is not known whether this finding from
studying heterogeneous patient groups is applicable to a particular surgical patient
population. We performed the present meta-analysis to determine whether anesthesia choice affected the outcome after elective total hip replacement (THR).
METHODS: Medline (1966 to August 2005), MD Consult (1966 to August 2005),
BIOSIS (1969 to August 2005), and EMBASE (1969 to August 2005) databases were
searched. Randomized and quasirandomized studies comparing GA and neuraxial
(spinal or epidural) block for elective THR were included in this analysis.
RESULTS: Ten independent trials, involving 330 patients under GA and 348 patients
under neuraxial block, were identified and analyzed. Pooled results from five trials
showed that neuraxial block significantly decreased the incidence of radiographically diagnosed deep venous thrombosis or pulmonary embolism. The odds ratio
(OR) for deep venous thrombosis was 0.27 with 95% confidence interval (CI)
0.17 0.42. The OR for pulmonary embolism was 0.26 with 95% CI 0.12 0.56.
Neuraxial block also decreased the operative time by 7.1 min/case (95% CI 2.311.9
min) and intraoperative blood loss by 275 mL/case (95% CI 180 371 mL). Data
from three trials showed that patients under neuraxial block for THR were less
likely to require blood transfusion than were patients under GA (21/177 12% vs
62/188 33% of patients transfused, P 0.001 by z-test). The OR for this
comparison was 0.26. However, the CIs were wide and compatible with both no
effect and a nine-tenths reduction (95% CI 0.06 1.05).
CONCLUSIONS: Patients undergoing elective THR under neuraxial anesthesia seem to
have better outcomes than those under GA.
(Anesth Analg 2006;103:1018 25)

ip replacement is a common orthopedic procedure, generally performed in elderly patients. In 2002,


343,000 patients underwent 345,000 hip replacement
procedures in the United States (1). Despite the common occurrence of this procedure, there is controversy
as to whether total hip replacement (THR) is best
performed under neuraxial block, including epidural
and spinal block, or general anesthesia (GA). In 2000,
Rodgers et al. (2) published a meta-analysis showing
that the use of neuraxial techniques for a variety of

From the Department of Anesthesiology, University of Virginia


Health System, Charlottesville, Virginia.
Accepted for publication June 5, 2006.
Supported by Department of Anesthesiology, University of
Virginia; and National Institute of Health Grants R01 GM065211
and R01 NS045983.
Address correspondence and reprint requests to Dr. Zhiyi Zuo,
Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 229080710. Address e-mail to zz3c@virginia.edu.
Copyright 2006 International Anesthesia Research Society
DOI: 10.1213/01.ane.0000237267.75543.59

1018

surgical procedures resulted in a decrease in mortality, venous thromboembolism, myocardial infarction,


and several other complications. However, they were
unable to draw conclusions regarding the validity of
these findings to specific surgical procedures or patient population. Previous work has shown that THR
under neuraxial blockade may be associated with less
deep venous thrombosis (DVT) (37) and pulmonary
embolism (PE) (35), and a reduced intraoperative
estimated blood loss and transfusion requirement
(3,711) when compared with those under GA. However, many of these studies are now approximately 20
yr old. Neuraxial block may also decrease the time
needed to discharge the patient from the postanesthesia care unit (12) and provide stable intraoperative
hemodynamics (13), but these benefits of neuraxial
block are not consistently shown in other studies
(7,13,14). In addition, many of these studies have been
hindered by relatively small cohorts of patients and, in
some cases, the relatively rare occurrence of clinically
significant morbidity. Thus, it has been difficult to
draw conclusions regarding the effects of anesthesia
choice on the outcomes for THR.
Vol. 103, No. 4, October 2006

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


Patient numbers
Source

Design

Neuraxial General

Outcome
measures

DVT
prophylaxis

Neuraxial
technique

Keith (1977) (11)

Randomized
prospective

10

Blood loss

Dextran given
postoperatively

Single-injection
epidural

Hole (1980) (14)

Randomized
prospective

29

31

Operative time,
PE, transfusion
volume, DVT

5000 units sc
heparin from
Day 17

Single-injection
epidural

Thorburn (1980) (6)

Quasirandomized
prospective

47

38

Blood loss,
transfusion
volume, DVT

Not noted

Spinal

Modig (1981) (3)

Randomized
prospective

15

15

DVT, PE, blood


loss, transfusion
volume,
operative time

None

Continuous
epidural for
24 h

Modig (1983) (4)

Quasirandomized
prospective

30

30

Blood loss, DVT,


PE, operative
time

None

Continuous
epidural for
24 h

Modig (1986) (5)

Prospective
randomized

48

46

Operative time,
blood loss,
DVT, PE

None

Continuous
epidural for
24 h

Davis (1987,
1989)a(7,16)

Randomized
prospective

69

71

DVT, PE,
hemostatic
markers,
operative time,
blood loss,
patients
transfused

Stockings

Spinal

Modig (1987) (17)

Randomized
prospective

14

10

Operative time,
blood loss

None

Continuous
epidural for
24 h

Borghi (2002,2005)b
(13,15)

Randomized
prospective

70

70

Hypotension,
bradycardia,
operative time,
intraoperative
blood losses,
patients
transfused

Not noted

Continuous
epidural

Brueckner
(2003) (18)

Randomized
prospective

16

10

Hemostatic
markers,
operative time,
transfusion
volume

Stockings and
low molecular
heparin
(madroparin)
given
preoperatively

Spinal

Davis et al. presented their final results from the same groups of patients in two publications in 1987 and 1989 (7,16).
Borghi et al. reported their findings from the same groups of patients in two papers published in 2002 and 2005 (13,15).

We performed this meta-analysis to test the hypothesis that elective THR under neuraxial block was associated with improved outcomes compared with the
surgery under GA. We focused our analysis on elective
THR to reduce many confounding factors, such as blood
loss before the procedure, in patients with hip fracture
and trauma. We chose to analyze intraoperative outcome measurements including operative time, estimated
intraoperative blood loss, and transfusion requirements
Vol. 103, No. 4, October 2006

and intra- and postoperative outcome measurements


such as number of patients with DVT, PE, and mortality.

METHODS
Medline (1966 to August 2005), MD Consult (1966
to August 2005), BIOSIS (1969 to August 2005), and
EMBASE (1969 to August 2005) databases were independently searched by two authors (WJM and AMS)
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Figure 1. Comparison of operative time for


elective total hip replacement under
neuraxial block versus under general anesthesia (GA). N number of patients.

using the following keywords: total hip replacement,


epidural anesthesia, spinal anesthesia, general anesthesia, hip fracture, deep venous thrombosis, regional
anesthesia, elective hip surgery, and pulmonary embolism. The terms epidural anesthesia, spinal anesthesia, and general anesthesia were linked with
or and combined using and with each subsequent
term. No language limits were used. Bibliographies
were also searched for relevant publications.
All publications found during the search were
manually and independently reviewed by the same
two authors. Randomized and quasirandomized studies comparing the outcomes of elective THR under
neuraxial block and GA were included in the analysis.
Quasirandomized studies are studies in which patients are assigned into study groups by alteration
based on variables such as surgical dates. Study
inclusion was limited to patient groups that underwent THR under either neuraxial block or GA. We did
not include patients who had THR under combined
techniques, nor did we include studies that compared
controlled hypotension patients under GA with patients under neuraxial block. The following outcome
data were extracted from each study if reported:
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Anesthesia Choice and Elective THR

estimated intraoperative blood loss, number of patients requiring blood transfusion and the transfusion
volume, operative time, number of patients with DVT
or PE who were diagnosed radiographically, and the
associated mortality. The decision on the suitability of
a study for our analysis and the extracted data by the
two reviewers/authors were compared. Discrepancy
among them was resolved by discussion and reconfirming the data in the original paper. We contacted
the authors if multiple publications on the subject
were from the same authors to verify that the data in
each of the multiple publications were from independent patient groups. Data of continuous parameters
must have been presented in numerical format in the
study to have been included in our analysis, whereas
the data in nontabular format (i.e., bar or line graphs)
were not included, as accurate numbers could not be
assured.
Meta-analysis was performed with the MedCalc
software (Mariakerke, Belgium). Patients who had GA
were treated as control groups, and patients with
neuraxial block were treated as intervention groups.
Odds ratio (OR) and 95% confidence intervals (CI)
were reported for dichotomous outcome parameters.
ANESTHESIA & ANALGESIA

Figure 2. Comparison of intraoperative


blood loss volume for elective total hip
replacement under neuraxial block versus
under general anesthesia (GA). N number of patients.

Standardized mean difference (SMD) and 95% CI


were presented for continuous outcome parameters.
Heterogeneity among studies was tested by 2 test.
The results for both the fixed effects model and the
random effects model were presented. The fixed effects
model assumes that all studies are from a common
population and that the effect size is not significantly
different among different trials. However, when there
was significant heterogeneity among the studies (P
0.05), we read the original studies again to identify
possible differences in study design (inclusion criteria
and exclusion criteria) and in the patient characteristics
(mean age and comorbidities) among the trials to determine whether we could separate trials into homogeneous groups. If this attempt failed to identify the cause
of the heterogeneity, results calculated by using the
random effects model are more appropriate because this
model incorporated both the random variation within
the studies and the variation among the different studies.

and narcotic consumption that are not included in our


analysis (12). Two papers of Borghi et al. published in
2002 (13) and 2005 (15) reported findings from the same
groups of patients. Although data of different outcome
variables were reported in these two papers and are
included in our analysis, we considered that these two
papers reported results from one study. Davis et al.
reported findings from a total of 140 patients in 1989 (7),
of which findings from the first 101 patients were
published in 1987 (9). However, the authors did not
report the intraoperative blood loss from the 140 patients
in the latter study (7). Instead, this result was presented
in the thesis submitted by F. Michael Davis for his MD
degree (16). These three publications are considered as
reports for one study. Thus, only 10 independent studies
had the relevant data for our analysis. These 10 studies
had a total of 330 patients undergoing GA and 348
patients undergoing neuraxial block. Characteristics of
these trials are displayed in Table 1. Among them, no
study presented data on mortality.

RESULTS
Our search identified 144 publications. Among them,
studies in 14 publications met the inclusion criteria. One
paper reported outcome measures such as pain scores
Vol. 103, No. 4, October 2006

Operative Times
Eight studies reported this outcome. Six of them
showed no statistical difference in operative times
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Figure 3. Comparison of number of patients


with blood transfusion for elective total hip
replacement under neuraxial block versus
under general anesthesia (GA). n number
of patients requiring blood transfusion;
N total number of patients in the study
group.

between neuraxial block and GA. Two studies showed


that the operative times of THR under neuraxial block
were shorter than those under GA (7,14). The pooled
data from the eight studies showed a statistically
significant decrease in operative time (Fig. 1). The
THR procedure under neuraxial block was finished
7.1 min (95% CI 2.311.9 min) sooner than the procedure performed under GA.

Intraoperative Blood Loss Volume


Eight studies reported intraoperative blood loss,
and six of them showed that neuraxial block significantly decreased blood loss compared with GA
(3 6,9,16). The pooled data from the eight studies
showed a statistically significant decrease in blood loss
in patients under neuraxial block versus GA (Fig. 2,
mean difference 275 mL/case and 95% CI 180 371 mL).

Number of Patients Requiring Blood Transfusions


Six studies reported data on number of patients
transfused and/or the blood transfusion volume.
Among the four studies that reported blood transfusion volume, two reported the volume in numerical
format. Meta-analysis was not performed with data
from these two studies because of the concern for too
few studies. One of the studies noted that neuraxial
block reduced blood transfusion volume per transfused patient when compared with GA (3). Among the
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Anesthesia Choice and Elective THR

three studies that reported number of patients transfused, one showed that neuraxial block significantly
reduced the number of patients requiring blood transfusion (6). The pooled data from these three studies
demonstrated that fewer patients were transfused
when THR was performed under neuraxial block
(21/177 12% patients) than that under GA
(62/188 33%, P 0.001 by z-test) (Fig. 3, OR 0.26).
However, the CIs were wide and compatible with
both no effect and a nine-tenths reduction (95% CI
0.06 1.05).

Deep Venous Thrombosis


Five studies included data on the number of patients who developed radiographically proven DVT.
All of them showed that neuraxial block significantly
decreased the incidence of DVT compared with GA
(37). The pooled data showed that significantly fewer
patients developed DVT when the THR was performed under neuraxial block (58/200 29% patients)
than under GA (116/209 56% patients) (Fig. 4, OR
0.27, 95% CI 0.17 0.42).

Pulmonary Embolism
Five studies presented data on the number of
patients who suffered from a PE evidenced by radiographic or nuclear medicine studies. Three of these
studies showed that neuraxial block significantly decreased the incidence of PE compared with GA (35).
ANESTHESIA & ANALGESIA

Figure 4. Comparison of number of patients


with deep venous thrombosis for elective
total hip replacement under neuraxial block
versus under general anesthesia (GA). n
number of patients with deep venous
thrombosis; N total number of patients in
the study group.

The other two studies did not show a significant


difference in the number of patients who suffered
from PE after THR under neuraxial block versus GA.
The pooled data showed that significantly fewer patients had PE when the THR was performed under
neuraxial block (14/191 7% patients) than under GA
(38/193 20% patients) (Fig. 5, OR 0.26, 95% CI
0.12 0.56).

DISCUSSION
Our meta-analysis showed statistically significant
reductions in the operative time, intraoperative blood
loss, and the incidence of DVT and PE when neuraxial
blockade was used in a specific patient population:
patients undergoing elective THR. Among the 10
independent studies that contributed data to our
analysis, three studies compared the outcomes between spinal anesthesia and GA (6,7,18), and the
others compared outcomes between epidural anesthesia and GA. In our analysis, we did not separate the
neuraxial block into spinal and epidural block subgroups because of the concern of small sample size for
each subgroup.
Our analysis may have limitations. All the data
included in our analysis are from published studies,
which may have produced biased results. However,
Vol. 103, No. 4, October 2006

funnel plots (plots are not shown) of sample size


versus OR or sample size versus smd for intraoperative blood loss, operative time, number of patients
transfused, and the incidence of DVT and PE did not
show evidence for significant publication bias. It
should be noted that funnel plots derived from a small
number of studies may not be a sensitive tool to detect
publication bias. It is also possible that our study
suffers from informed censoring. This refers to a
situation in which the authors of original studies
collected data on all our selected outcome variables
but failed to report on results that were not different
between the groups or were not interesting to the
authors. We could not use these data in our analysis.
As a result, the estimated differences between patient
groups by meta-analysis are likely to be more than the
actual differences. To reduce this possibility, we attempted to contact the authors of all trials included in
this analysis to forward any outcome data they had on
record that were not reported in their original papers.
There may also have been selection bias. We included
all identified studies that were prospective, randomized, or quasirandomized trials comparing neuraxial
block versus GA for elective THR. Thus, selection bias
in our analysis may be small. Lastly, our analysis is
hindered by the datedness of the studies contributing
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Figure 5. Comparison of number of patients


with pulmonary embolism for elective total
hip replacement under neuraxial block versus under general anesthesia (GA). n
number of patients with pulmonary embolism; N total number of patients in the
study group.

to the analysis. Some aspects of these studies do not


reflect current practice patterns. For example, pharmacologic prophylaxis for DVT is currently used for
patients after THR. Most of the patients in our analysis
did not receive this therapy. This issue will be discussed further in Thromboembolic Events.

Operative Times
Concerns over the use of neuraxial block include a
potentially delayed start time of surgery due to the
placement of the block, failure of the block with
subsequent conversion to GA, and potentially less
than optimal muscle relaxation, which some orthopedic surgeons believe will make the dissection and
placement of the prosthesis more difficult. Our data
indicate a small reduction in the operative time for
elective THR using neuraxial block when compared
with GA. Our data are consistent with a recent Cochrane Report on hip fracture patients by Parker et al.
(19) in which anesthesia choice had a minimal effect
on operative times. Although we were able to show a
statistically significant decrease in operative times
when THR was performed under neuraxial blockade,
the average decrease in duration of 7.1 min/case is
likely not clinically significant.
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Anesthesia Choice and Elective THR

Intraoperative Blood Loss and Incidence of


Blood Transfusion
The potential for decreasing intraoperative blood
loss is an often quoted advantage for performing THR
under neuraxial anesthesia. In this meta-analysis, we
showed a statistically significant decrease in blood
loss in the neuraxial block group. Although the mean
decrease was only 275 mL, this amount may be
clinically significant, as neuraxial blockade also decreased the number of patients requiring intraoperative blood transfusion (12% patients under neuraxial
blockade versus 33% patients under GA).

Thromboembolic Events (DVT and PE)


PE remains a potentially catastrophic complication
of THR with a reported incidence of clinical PE in
0.2%2.0% of patients (20). The incidence of DVT is
around 1%10% now, but was as high as 40% 60% in
some series where DVT prophylaxis was not used
(21). This meta-analysis shows a significant reduction in
the number of patients developing DVT (29% vs 56%)
and PE (7% vs 20%) when neuraxial anesthesia is used
for THR. The authors in these series actively searched for
PE and DVT using the combinations of phlebography,
plethysmography, venography, ventilation/perfusions
scans, and fibrinogen uptake tests. Our finding that
neuraxial block decreases the incidence of DVT and PE is
ANESTHESIA & ANALGESIA

consistent with the data published by Rodgers et al. (2)


involving nearly 10,000 patients and showed that
neuraxial blocks for a variety of surgeries decreased
DVT by 44% and PE by 55%.
Regardless of the causes for the decreased incidences of DVT and PE by neuraxial block, the implication of our findings must be viewed cautiously.
Only one of the studies reviewed here used pharmacologic DVT prophylaxis, and interestingly, that study
showed no significant difference in the rate of DVT
between the two groups (14). For the last 15 yr,
pharmacologic DVT prophylaxis has been a component of the standard of care for THR patients. Although neuraxial blockade apparently decreases the
risk of DVT when no chemical prophylaxis is used, it
is not as effective as using low-molecular-weight
heparin (22). Four of the studies reviewed here used
epidural catheters for postoperative analgesia (35,17).
The fact that most of these studies were performed
before the use of DVT prophylaxis was the standard of
care poses a significant limitation in the application of
our findings to todays practice. It remains to be seen
whether or not the effects of a single-injection
neuraxial technique followed by postoperative pharmacologic anticoagulation would be additive in the
prevention of DVT and PE. These studies are needed
before we can determine whether neuraxial block
indeed reduces the incidence of DVT and PE after
THR in our current practice.
In summary, we analyzed the literature to determine whether anesthesia choice will affect the outcome of a specific surgical patient population: patients
undergoing elective THR. Our data indicate that
neuraxial block is associated with a decrease in intraoperative blood loss and the number of patients
requiring blood transfusions. It is not known whether
some of the beneficial effects such as reduced incidence of DVT and PE provided by neuraxial block are
applicable to todays practice when compared with
investigations performed 20 years ago. However, our
findings indicate that neuraxial block should be considered as a valid and potentially beneficial technique
for elective THR. Our analysis also points out the need
for further studies designed to investigate the effects
of anesthetic choice on outcomes for THR in the
context of current clinical practice, as many improvements in surgical and anesthetic techniques and postoperative care have evolved since these early studies
were performed.
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