Mauermann, William J. MD; Shilling, Ashley M. MD; Zuo, Zhiyi MD, PhD
Section Editor(s): Horlocker, Terese T.
Hip 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 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) (3–7) and pulmonary embolism (PE) (3–5), and a reduced intraoperative estimated blood loss and transfusion requirement (3,7–11) 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.
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 and intra- and postoperative outcome measurements such as number of patients with DVT, PE, and mortality.
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) 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: 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. Standardized mean difference (SMD) and 95% CI were presented for continuous outcome parameters. Heterogeneity among studies was tested by χ2 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.
Our search identified 144 publications. Among them, studies in 14 publications met the inclusion criteria. One paper reported outcome measures such as pain scores 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.
Eight studies reported this outcome. Six of them showed no statistical difference in operative times 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 2.3–11.9 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 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 (3–7). 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).
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 (3–5). 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).
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, 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 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.
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.
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 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 (3–5,17). 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 today's 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 today's 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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