a comparison of neuraxial block versus general.42

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Regional AnesthesiaSection Editor: Terese T. Horlocker

A Comparison of Neuraxial Block Versus GeneralAnesthesia 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 anesthe-sia (GA), neuraxial block reduced many serious complications in patients under-going various types of surgeries. It is not known whether this finding fromstudying heterogeneous patient groups is applicable to a particular surgical patientpopulation. We performed the present meta-analysis to determine whether anes-thesia 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 weresearched. 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 patientsunder neuraxial block, were identified and analyzed. Pooled results from five trials

showed that neuraxial block significantly decreased the incidence of radiographi-cally diagnosed deep venous thrombosis or pulmonary embolism. The odds ratio(OR) for deep venous thrombosis was 0.27 with 95% confidence interval (CI)0.170.42. The OR for pulmonary embolism was 0.26 with 95% CI 0.120.56.Neuraxial block also decreased the operative time by 7.1 min/case (95% CI 2.311.9min) and intraoperative blood loss by 275 mL/case (95% CI 180371 mL). Datafrom three trials showed that patients under neuraxial block for THR were lesslikely to require blood transfusion than were patients under GA (21/177 12% vs62/188 33% of patients transfused, P 0.001 by z-test). The OR for thiscomparison was 0.26. However, the CIs were wide and compatible with both noeffect and a nine-tenths reduction (95% CI 0.061.05).CONCLUSIONS:Patients undergoing elective THR under neuraxial anesthesia seem tohave better outcomes than those under GA.(Anesth Analg 2006;103:101825)

Hip replacement is a common orthopedic proce-dure, generally performed in elderly patients. In 2002,343,000 patients underwent 345,000 hip replacementprocedures in the United States (1). Despite the com-mon occurrence of this procedure, there is controversyas to whether total hip replacement (THR) is bestperformed under neuraxial block, including epiduraland spinal block, or general anesthesia (GA). In 2000,Rodgers et al. (2) published a meta-analysis showingthat the use of neuraxial techniques for a variety of

surgical procedures resulted in a decrease in mortal-ity, venous thromboembolism, myocardial infarction,and several other complications. However, they wereunable to draw conclusions regarding the validity ofthese findings to specific surgical procedures or pa-tient population. Previous work has shown that THRunder neuraxial blockade may be associated with lessdeep venous thrombosis (DVT) (37) and pulmonaryembolism (PE) (35), and a reduced intraoperativeestimated blood loss and transfusion requirement(3,711) when compared with those under GA. How-ever, many of these studies are now approximately 20yr old. Neuraxial block may also decrease the timeneeded to discharge the patient from the postanesthe-sia care unit (12) and provide stable intraoperativehemodynamics (13), but these benefits of neuraxial

block are not consistently shown in other studies(7,13,14). In addition, many of these studies have beenhindered by relatively small cohorts of patients and, insome cases, the relatively rare occurrence of clinicallysignificant morbidity. Thus, it has been difficult to

draw conclusions regarding the effects of anesthesiachoice on the outcomes for THR.

From the Department of Anesthesiology, University of VirginiaHealth System, Charlottesville, Virginia.

Accepted for publication June 5, 2006.

Supported by Department of Anesthesiology, University ofVirginia; and National Institute of Health Grants R01 GM065211and R01 NS045983.

Address correspondence and reprint requests to Dr. Zhiyi Zuo,Department of Anesthesiology, University of Virginia Health Sys-tem, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710. Address e-mail to [email protected].

Copyright 2006 International Anesthesia Research Society

DOI: 10.1213/01.ane.0000237267.75543.59

Vol. 103, No. 4, October 20061018


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We performed this meta-analysis to test the hypoth-esis that elective THR under neuraxial block was asso-ciated with improved outcomes compared with thesurgery under GA. We focused our analysis on electiveTHR to reduce many confounding factors, such as bloodloss before the procedure, in patients with hip fractureand trauma. We chose to analyze intraoperative out-

come measurements including operative time, estimatedintraoperative blood loss, and transfusion requirements

and intra- and postoperative outcome measurementssuch as number of patients with DVT, PE, and mortality.

METHODS

Medline (1966 to August 2005), MD Consult (1966to August 2005), BIOSIS (1969 to August 2005), and

EMBASE (1969 to August 2005) databases were inde-pendently searched by two authors (WJM and AMS)

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

Source Design

Patient numbersOutcomemeasures

DVTprophylaxis

NeuraxialtechniqueNeuraxial General

Keith (1977) (11) Randomizedprospective

10 9 Blood loss Dextran givenpostoperatively

Single-injectionepidural

Hole (1980) (14) Randomizedprospective

29 31 Operative time,PE, transfusion

volume, DVT

5000 units scheparin from

Day 17

Single-injectionepidural

Thorburn (1980) (6) Quasirandomizedprospective

47 38 Blood loss,transfusionvolume, DVT

Not noted Spinal

Modig (1981) (3) Randomizedprospective

15 15 DVT, PE, bloodloss, transfusionvolume,operative time

None Continuousepidural for24 h

Modig (1983) (4) Quasirandomizedprospective

30 30 Blood loss, DVT,PE, operativetime


Modig (1986) (5) Prospectiverandomized

48 46 Operative time,blood loss,DVT, PE


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

Randomizedprospective

69 71 DVT, PE,hemostaticmarkers,operative time,blood loss,patientstransfused

Stockings Spinal

Modig (1987) (17) Randomizedprospective

14 10 Operative time,blood loss


Borghi (2002,2005)b

(13,15)Randomized

prospective70 70 Hypotension,

bradycardia,operative time,intraoperativeblood losses,patientstransfused

Not noted Continuousepidural

Brueckner(2003) (18)

Randomizedprospective

16 10 Hemostaticmarkers,operative time,transfusion

volume

Stockings andlow molecularheparin(madroparin)

givenpreoperatively

Spinal

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

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using the following keywords: total hip replacement,epidural anesthesia, spinal anesthesia, general anes-thesia, hip fracture, deep venous thrombosis, regionalanesthesia, elective hip surgery, and pulmonary em-

bolism. The terms epidural anesthesia, spinal an-esthesia, and general anesthesia were linked withor and combined using and with each subsequentterm. No language limits were used. Bibliographieswere also searched for relevant publications.

All publications found during the search were

manually and independently reviewed by the sametwo authors. Randomized and quasirandomized stud-ies comparing the outcomes of elective THR underneuraxial block and GA were included in the analysis.Quasirandomized studies are studies in which pa-tients are assigned into study groups by alteration

based on variables such as surgical dates. Studyinclusion was limited to patient groups that under-went THR under either neuraxial block or GA. We didnot include patients who had THR under combinedtechniques, nor did we include studies that comparedcontrolled hypotension patients under GA with pa-

tients under neuraxial block. The following outcomedata were extracted from each study if reported:

estimated intraoperative blood loss, number of pa-tients requiring blood transfusion and the transfusionvolume, operative time, number of patients with DVTor PE who were diagnosed radiographically, and theassociated mortality. The decision on the suitability ofa study for our analysis and the extracted data by thetwo reviewers/authors were compared. Discrepancyamong them was resolved by discussion and recon-firming the data in the original paper. We contactedthe authors if multiple publications on the subject

were from the same authors to verify that the data ineach of the multiple publications were from indepen-dent patient groups. Data of continuous parametersmust have been presented in numerical format in thestudy to have been included in our analysis, whereasthe data in nontabular format (i.e., bar or line graphs)were not included, as accurate numbers could not beassured.

Meta-analysis was performed with the MedCalcsoftware (Mariakerke, Belgium). Patients who had GAwere treated as control groups, and patients withneuraxial block were treated as intervention groups.

Odds ratio (OR) and 95% confidence intervals (CI)were reported for dichotomous outcome parameters.

Figure 1. Comparison of operative time forelective total hip replacement underneuraxial block versus under general anes-thesia (GA). N number of patients.

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Standardized mean difference (SMD) and 95% CIwere presented for continuous outcome parameters.Heterogeneity among studies was tested by 2 test.The results for both the fixed effects model and therandom effects model were presented. The fixed effectsmodel assumes that all studies are from a commonpopulation and that the effect size is not significantlydifferent among different trials. However, when therewas significant heterogeneity among the studies (P 0.05), we read the original studies again to identifypossible differences in study design (inclusion criteriaand exclusion criteria) and in the patient characteristics(mean age and comorbidities) among the trials to deter-mine whether we could separate trials into homoge-neous groups. If this attempt failed to identify the causeof the heterogeneity, results calculated by using therandom effects model are more appropriate because thismodel incorporated both the random variation withinthe studies and the variation among the different studies.

RESULTS

Our search identified 144 publications. Among them,

studies in 14 publications met the inclusion criteria. Onepaper reported outcome measures such as pain scores

and narcotic consumption that are not included in ouranalysis (12). Two papers of Borghi et al. published in2002 (13) and 2005 (15) reported findings from the samegroups of patients. Although data of different outcomevariables were reported in these two papers and areincluded in our analysis, we considered that these twopapers 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 werepublished in 1987 (9). However, the authors did notreport the intraoperative blood loss from the 140 patientsin the latter study (7). Instead, this result was presentedin the thesis submitted by F. Michael Davis for his MDdegree (16). These three publications are considered asreports for one study. Thus, only 10 independent studieshad the relevant data for our analysis. These 10 studieshad a total of 330 patients undergoing GA and 348patients undergoing neuraxial block. Characteristics ofthese trials are displayed in Table 1. Among them, nostudy presented data on mortality.

Operative Times

Eight studies reported this outcome. Six of themshowed no statistical difference in operative times

Figure 2. Comparison of intraoperativeblood loss volume for elective total hipreplacement under neuraxial block versusunder general anesthesia (GA). N num-ber of patients.



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between neuraxial block and GA. Two studies showedthat the operative times of THR under neuraxial block

were shorter than those under GA (7,14). The pooleddata from the eight studies showed a statisticallysignificant decrease in operative time (Fig. 1). TheTHR procedure under neuraxial block was finished7.1 min (95% CI 2.311.9 min) sooner than the proce-dure performed under GA.

Intraoperative Blood Loss Volume

Eight studies reported intraoperative blood loss,and six of them showed that neuraxial block signifi-cantly decreased blood loss compared with GA(36,9,16). The pooled data from the eight studies

showed a statistically significant decrease in blood lossin patients under neuraxial block versus GA (Fig. 2,mean difference 275 mL/case and 95% CI 180371 mL).

Number of Patients Requiring Blood TransfusionsSix studies reported data on number of patients

transfused and/or the blood transfusion volume.Among the four studies that reported blood transfu-sion volume, two reported the volume in numericalformat. Meta-analysis was not performed with datafrom these two studies because of the concern for toofew studies. One of the studies noted that neuraxial

block reduced blood transfusion volume per trans-fused patient when compared with GA (3). Among the

three studies that reported number of patients trans-fused, one showed that neuraxial block significantly

reduced the number of patients requiring blood trans-fusion (6). The pooled data from these three studiesdemonstrated that fewer patients were transfusedwhen 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% CI0.061.05).

Deep Venous ThrombosisFive studies included data on the number of pa-

tients who developed radiographically proven DVT.

All of them showed that neuraxial block significantlydecreased the incidence of DVT compared with GA(37). The pooled data showed that significantly fewerpatients developed DVT when the THR was per-formed under neuraxial block (58/200 29% patients)than under GA (116/209 56% patients) (Fig. 4, OR0.27, 95% CI 0.170.42).

Pulmonary EmbolismFive studies presented data on the number of

patients who suffered from a PE evidenced by radio-graphic or nuclear medicine studies. Three of these

studies showed that neuraxial block significantly de-creased the incidence of PE compared with GA (35).

Figure 3.Comparison of number of patientswith blood transfusion for elective total hipreplacement under neuraxial block versusunder general anesthesia (GA). n numberof patients requiring blood transfusion;N total number of patients in the studygroup.



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The other two studies did not show a significantdifference in the number of patients who sufferedfrom PE after THR under neuraxial block versus GA.The pooled data showed that significantly fewer pa-tients had PE when the THR was performed underneuraxial block (14/191 7% patients) than under GA(38/193 20% patients) (Fig. 5, OR 0.26, 95% CI0.120.56).

DISCUSSION

Our meta-analysis showed statistically significantreductions in the operative time, intraoperative blood

loss, and the incidence of DVT and PE when neuraxialblockade was used in a specific patient population:patients undergoing elective THR. Among the 10independent studies that contributed data to ouranalysis, three studies compared the outcomes be-tween spinal anesthesia and GA (6,7,18), and theothers compared outcomes between epidural anesthe-sia and GA. In our analysis, we did not separate theneuraxial block into spinal and epidural block sub-groups because of the concern of small sample size foreach subgroup.

Our analysis may have limitations. All the data

included in our analysis are from published studies,which may have produced biased results. However,

funnel plots (plots are not shown) of sample sizeversus OR or sample size versus smdfor intraopera-tive blood loss, operative time, number of patientstransfused, and the incidence of DVT and PE did notshow evidence for significant publication bias. Itshould be noted that funnel plots derived from a smallnumber of studies may not be a sensitive tool to detectpublication bias. It is also possible that our studysuffers from informed censoring. This refers to asituation in which the authors of original studiescollected data on all our selected outcome variables

but failed to report on results that were not differentbetween the groups or were not interesting to theauthors. We could not use these data in our analysis.As a result, the estimated differences between patientgroups by meta-analysis are likely to be more than theactual differences. To reduce this possibility, we at-tempted to contact the authors of all trials included inthis analysis to forward any outcome data they had onrecord that were not reported in their original papers.There may also have been selection bias. We includedall identified studies that were prospective, random-ized, or quasirandomized trials comparing neuraxial

block versus GA for elective THR. Thus, selection bias

in our analysis may be small. Lastly, our analysis ishindered by the datedness of the studies contributing

Figure 4.Comparison of number of patientswith deep venous thrombosis for electivetotal hip replacement under neuraxial blockversus under general anesthesia (GA). n number of patients with deep venousthrombosis;N total number of patients inthe study group.



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to the analysis. Some aspects of these studies do not

reflect current practice patterns. For example, pharma-cologic prophylaxis for DVT is currently used forpatients after THR. Most of the patients in our analysisdid not receive this therapy. This issue will be dis-cussed further in Thromboembolic Events.

Operative Times

Concerns over the use of neuraxial block include apotentially delayed start time of surgery due to theplacement of the block, failure of the block withsubsequent conversion to GA, and potentially less

than optimal muscle relaxation, which some orthope-dic surgeons believe will make the dissection andplacement of the prosthesis more difficult. Our dataindicate a small reduction in the operative time forelective THR using neuraxial block when comparedwith GA. Our data are consistent with a recent Co-chrane Report on hip fracture patients by Parker et al.(19) in which anesthesia choice had a minimal effecton operative times. Although we were able to show astatistically significant decrease in operative timeswhen THR was performed under neuraxial blockade,

the average decrease in duration of 7.1 min/case islikely not clinically significant.

Intraoperative Blood Loss and Incidence of

Blood TransfusionThe potential for decreasing intraoperative blood

loss is an often quoted advantage for performing THRunder neuraxial anesthesia. In this meta-analysis, weshowed a statistically significant decrease in bloodloss in the neuraxial block group. Although the meandecrease was only 275 mL, this amount may beclinically significant, as neuraxial blockade also de-creased the number of patients requiring intraopera-tive blood transfusion (12% patients under neuraxial

blockade versus 33% patients under GA).

Thromboembolic Events (DVT and PE)PE remains a potentially catastrophic complicationof THR with a reported incidence of clinical PE in0.2%2.0% of patients (20). The incidence of DVT isaround 1%10% now, but was as high as 40%60% insome series where DVT prophylaxis was not used(21). This meta-analysis shows a significant reduction inthe number of patients developing DVT (29% vs 56%)and PE (7% vs 20%) when neuraxial anesthesia is usedfor THR. The authors in these series actively searched forPE and DVT using the combinations of phlebography,plethysmography, venography, ventilation/perfusions

scans, and fibrinogen uptake tests. Our finding thatneuraxial block decreases the incidence of DVT and PE is

Figure 5.Comparison of number of patientswith pulmonary embolism for elective totalhip replacement under neuraxial block ver-sus under general anesthesia (GA). n number of patients with pulmonary embo-lism; N total number of patients in thestudy group.



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consistent with the data published by Rodgers et al. (2)involving nearly 10,000 patients and showed thatneuraxial blocks for a variety of surgeries decreasedDVT by 44% and PE by 55%.

Regardless of the causes for the decreased inci-dences of DVT and PE by neuraxial block, the impli-cation of our findings must be viewed cautiously.Only one of the studies reviewed here used pharma-cologic DVT prophylaxis, and interestingly, that study

showed no significant difference in the rate of DVTbetween the two groups (14). For the last 15 yr,pharmacologic DVT prophylaxis has been a compo-nent of the standard of care for THR patients. Al-though neuraxial blockade apparently decreases therisk of DVT when no chemical prophylaxis is used, itis not as effective as using low-molecular-weightheparin (22). Four of the studies reviewed here usedepidural catheters for postoperative analgesia (35,17).The fact that most of these studies were performed

before the use of DVT prophylaxis was the standard ofcare poses a significant limitation in the application of

our findings to todays practice. It remains to be seenwhether or not the effects of a single-injectionneuraxial technique followed by postoperative phar-macologic anticoagulation would be additive in theprevention of DVT and PE. These studies are needed

before we can determine whether neuraxial blockindeed reduces the incidence of DVT and PE afterTHR in our current practice.

In summary, we analyzed the literature to deter-mine whether anesthesia choice will affect the out-come of a specific surgical patient population: patientsundergoing elective THR. Our data indicate that

neuraxial block is associated with a decrease in intra-operative blood loss and the number of patientsrequiring blood transfusions. It is not known whethersome of the beneficial effects such as reduced inci-dence of DVT and PE provided by neuraxial block areapplicable to todays practice when compared withinvestigations performed 20 years ago. However, ourfindings indicate that neuraxial block should be con-sidered as a valid and potentially beneficial techniquefor elective THR. Our analysis also points out the needfor further studies designed to investigate the effectsof anesthetic choice on outcomes for THR in the

context of current clinical practice, as many improve-ments in surgical and anesthetic techniques and post-operative care have evolved since these early studieswere performed.

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