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Review Article  |   November 2005
Efficacy of Postoperative Patient-controlled and Continuous Infusion Epidural Analgesia versus  Intravenous Patient-controlled Analgesia with Opioids: A Meta-analysis
Author Affiliations & Notes
  • Christopher L. Wu, M.D.
    *
  • Seth R. Cohen, B.S.
  • Jeffrey M. Richman, M.D.
  • Andrew J. Rowlingson, B.A.
    §
  • Genevieve E. Courpas, B.A.
    §
  • Kristin Cheung, M.D.
  • Elaina E. Lin, B.A.
    #
  • Spencer S. Liu, M.D.
    **
  • * Associate Professor, ‡ Assistant Professor, § Research Associate, ∥ Senior Instructor, # Medical Student, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, Maryland. † Medical Student, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania. ** Clinical Professor, Department of Anesthesiology, Virginia Mason Medical Center, University of Washington, Seattle, Washington.
Article Information
Review Article / Pain Medicine
Review Article   |   November 2005
Efficacy of Postoperative Patient-controlled and Continuous Infusion Epidural Analgesia versus  Intravenous Patient-controlled Analgesia with Opioids: A Meta-analysis
Anesthesiology 11 2005, Vol.103, 1079-1088. doi:
Anesthesiology 11 2005, Vol.103, 1079-1088. doi:
DESPITE the availability of postoperative pain guidelines,1 postoperative pain continues to be undertreated2,3 and may result in a variety of unfavorable short- and long-term outcomes.4–6 Of the two major analgesic options (epidural analgesia vs.  systemic opioids) after inpatient surgery, the overall benefits of postoperative epidural analgesia on mortality and major morbidity are controversial with available larger observational, randomized controlled trials and meta-analyses equivocal for the efficacy of epidural analgesia in improving perioperative outcomes.7–14 However, systematic analysis of available nonrandomized and randomized trials15,16 seem to indicate that postoperative epidural analgesia will provide superior analgesia when compared with that from systemic opioids.
Even though epidural analgesia seems to provide better postoperative pain control than systemic opioids, this comparison in some sense may not be meaningful because categorizing systemic opioids (which includes intramuscular, subcutaneous, intravenous, and intravenous patient-controlled analgesia [PCA]) into a single generic entity may not reflect the actual clinical use of postoperative opioids, which may be primarily delivered via  intravenous PCA.1,17,18 To truly determine the analgesic value of epidural analgesia for postoperative pain management, it would be appropriate to compare patient-controlled epidural analgesia (PCEA) with intravenous PCA, which many believe is the accepted standard for delivery of opioid analgesia postoperatively. We performed a meta-analysis of the analgesic efficacy of postoperative PCEA and continuous epidural infusion (CEI) analgesia to intravenous PCA with opioid. To minimize duplication of data and results from our previous publication,15 we used a different literature search strategy and attempted to acquire additional unpublished data from studies that had not been available for our previous meta-analysis.
Materials and Methods
The National Library of Medicine’s PubMed database was searched for the time period 1966 to August 4, 2004. PubMed was searched for all articles containing text words PCA  or patient-controlled analgesia  (9,122 articles), which was combined with the text word epidural  (25,480 articles) using the usual Boolean meanings of AND  . The result was 757 articles. This search was limited to the English language (650 articles) and then the Randomized Controlled Trials function, which resulted in 299 abstracts. The full article of each of the 299 abstracts was then reviewed by one of the authors for inclusion into the meta-analysis. No minimum sample sizes were invoked for inclusion of studies in the analysis. Any disputes were resolved by agreement of at least two reviewers. After selecting the initial articles, the authors’ personal files were checked for any additional studies.
For the purposes of this meta-analysis, postoperative epidural analgesia was defined as a primarily local anesthetic or opioid-based analgesic regimen delivered into the epidural space by CEI or PCEA over at least a 24-h period after a surgical procedure. Patient-controlled analgesia was defined as delivery of analgesic medication either through the epidural or intravenous catheter via  a mechanical PCA device. Only studies that compared postoperative epidural versus  intravenous PCA with opioids using visual analog scale (VAS) measurements of pain or a similar substitute (e.g.  , numerical rating scale) in a randomized fashion were included. Only studies including primarily only adult patients (aged ≥ 18 yr) were allowed. To be included in this meta-analysis, studies had to have a clear comparison between epidural analgesia to intravenous PCA without any crossover or concurrent use of the alternate regimen (e.g.  , concurrent use of intravenous PCA during a dose-finding study of postoperative epidural analgesia, which might include a normal saline epidural control group). Exclusion criteria included articles where VAS pain scores could not be recorded or extrapolated from the data provided in the article. Studies of epidural analgesia that only gave a single epidural dose at the time of surgery (single shot) or by repeated healthcare provider epidural bolus dosing were not included.
Data (e.g.  , VAS pain scores, number of subjects, type of epidural regimen, study characteristics) were abstracted from each article, and the results were recorded. Data were extrapolated from figures as needed; however, an attempt was made to contact the original authors before extrapolation. Definition of complications was recorded as originally defined by the study. We then recorded the incidence of that complication as reported by the study. For nausea and vomiting, we recorded the higher number if both were reported. In some cases, we could not translate a study’s data into an incidence rate. In those studies, we did not enter that data into the database; however, we did incorporate the remainder of that study’s data as feasible. For incomplete or uninterpretable data, we made an attempt to contact the corresponding author of the study in question.
All reported data were included as unique observations and subgrouped as described below. VAS or numeric pain scores were converted to a 0–10 scale. VAS data were weighted by sample size and, if a given article measured pain at multiple time points, all measurements were included in the analysis. Therefore, the n reported is the total number of patient observations (i.e.  , one study of 10 patients that measured pain at 3 different time points would contribute an n of 30 to the overall sample size). The global mean VAS (weighted for patient observations) and for each postoperative day up to 3 days after surgery between epidural analgesia and intravenous PCA were compared. The data for epidural analgesia were subdivided by type of delivery (CEI vs.  PCEA), analgesic regimen, and location/type of surgery, with a subsequent comparison of the epidural analgesia to intravenous PCA performed. All epidural infusions containing local anesthetic were considered equivalent, including those with and without opioid. Both rest and incident (activity) pain were included in the global analysis; however, rest and incident pain were also analyzed separately and again divided into subgroups depending on various epidural characteristics as described above. Finally, the presence of minor complications (i.e.  , nausea or vomiting [whichever was more frequent], sedation, pruritus, urinary retention, and motor block/weakness) were recorded.
A fixed effect model was used. The level of significance for all tests was set at an α of 0.05. A Kolmogorov test showed that the data were not normally distributed; instead, both epidural and intravenous PCA opioid data were positively skewed. Analysis of variance was used to compare VAS pain scores between treatment groups. The Bonferroni correction was used for multiple comparisons of postoperative day VAS data. For complication data, comparisons were made between two groups at a time with the chi-square test. All statistical analyses were performed with SPSS 11.5.1 (SPSS Inc., Chicago, IL). After the data compilation was complete, we performed further analyses to assess the validity of our conclusions. We performed an analysis of the file drawer problem (i.e.  , how many unpublished studies or subjects showing no difference between treatment regimens would be needed to be “discovered” in someone’s file drawer to invalidate our results) as described by Rosenthal.19 
Results
The search resulted in 299 abstracts of which a total of 48 articles met all inclusion criteria. An additional 2 references from previous systematic reviews and other sources were also included, for a total of 50 articles (1). There were a total of 1,625 patients randomly assigned to epidural analgesia and 1,583 patients to intravenous PCA. A total of 251 articles were rejected for the following reasons: 235 were not comparisons of postoperative epidural analgesia versus  intravenous PCA as defined in the Materials and Methods, 2 were not randomized, 4 did not report usable VAS or numeric pain scores, and 10 included pediatric subjects. The characteristics of included studies are shown in table 1. Articles measured pain after a wide variety of operations and came from medical centers all over the world. Pain was measured after abdominal surgery in 19 studies (38%), with thoracic (n = 10, or 20%) and lower extremity (n = 7, or 14%) surgery being the next most common types of surgery studied. Only 4% of the epidural patients received local anesthetic alone, whereas 28% (n = 14) received opioids alone and 68% (n = 34) received local anesthetic and opioid, with the choice of epidural opioid being predominantly fentanyl (38%), followed by morphine (24%) and sufentanil (16%). The most commonly used epidural local anesthetic was bupivacaine (48%), followed by ropivacaine (18%). For intravenous PCA, morphine (76%) was most commonly used, followed by fentanyl (6%).
Table 1. Characteristics of Included Studies 
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Table 1. Characteristics of Included Studies 
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When all studies and observations were combined (table 2), epidural analgesia overall provided superior postoperative analgesia compared with intravenous PCA with opioids (P  < 0.001). Epidural analgesia provided significantly superior analgesia overall, for pain at rest, and for pain with activity (P  < 0.001). The quality of analgesia may be different at different points in the postoperative recovery period, so pain scores were also assessed at different postoperative times. Epidural analgesia overall was superior to intravenous PCA opioid analgesia at all time points (P  < 0.001 for each day up to 3 days after surgery) even when analyzed separately by pain at rest or pain with activity (table 2).
Table 2. Aggregate VAS Pain Data 
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Table 2. Aggregate VAS Pain Data 
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Table 3shows the VAS pain scores for CEI (n = 1,272 subjects) versus  PCEA (n = 353 subjects) versus  intravenous PCA (n = 1,583 subjects). For all epidural (CEI or PCEA) comparisons versus  intravenous PCA overall and for pain at rest and with activity, epidural analgesia provided significantly superior analgesia versus  intravenous PCA with opioids (P  < 0.001). When CEI was compared with PCEA, CEI provided significantly superior analgesia (P  < 0.001) versus  PCEA for overall pain, pain at rest, and pain with activity (table 3).
Table 3. PCEA VAS Pain Data 
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Table 3. PCEA VAS Pain Data 
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When comparing the different types of epidural regimens (opioid alone [hydrophilic vs.  lipophilic]vs.  local anesthetic + opioid vs.  local anesthetic alone), all epidural regimens provided significantly superior analgesia versus  intravenous PCA for overall pain, pain at rest, and pain with activity (table 4), with the exception of hydrophilic opioid–only regimens, which were primarily delivered via  a PCA device. Compared with local anesthetic alone or local anesthetic plus opioid, epidural hydrophilic opioid alone provided significantly inferior analgesia (P  < 0.001), but epidural lipophilic opioid alone provided comparable VAS scores overall and for pain with activity. Epidural local anesthetic plus opioid provided statistically equivalent analgesia (vs.  epidural local anesthetic alone) for overall pain and pain with activity but inferior analgesia for pain at rest as compared with local anesthetic alone (table 4).
Table 4. Epidural Analgesic Data 
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Table 4. Epidural Analgesic Data 
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Finally, epidural analgesia overall provided significantly superior analgesia (P  < 0.001) compared with intravenous PCA with opioids for all regions of surgery examined (thoracic, pelvic, abdominal, cesarean delivery, lower extremity, and multiple locations) (table 5). Studies where location of surgery was defined as “other” or “not specified” (n < 110 weighted observations for each group) were not included in these analyses. Rates for complications are shown in table 6. Compared with intravenous PCA, the epidural group had a lower incidence of nausea–vomiting and sedation but a higher incidence of pruritus, urinary retention, and motor block. When comparing CEI with PCEA, CEI provided statistically significantly superior analgesia (P  < 0.001) versus  PCEA for overall pain, pain at rest, and pain with activity; however, patients receiving CEI had a significantly higher incidence of nausea–vomiting and motor block but lower incidence of pruritus. Within the epidural group, the majority of the subjects with motor block received CEI. Finally, we calculated the number of file drawer subjects needed to invalidate our results to be 2,567 subjects.
Table 5. Analgesia by Region of Surgery 
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Table 5. Analgesia by Region of Surgery 
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Table 6. Complication Rates 
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Table 6. Complication Rates 
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Discussion
Although epidural analgesia has been shown to provide superior analgesia compared with systemic opioids in systematic reviews,15,16 the analgesic efficacy of PCEA or CEI compared with the accepted standard, intravenous PCA, has not been separately assessed. We performed a meta-analysis of randomized controlled trials and found that when compared with intravenous PCA, PCEA and CEI overall provided significantly superior postoperative analgesia at all time intervals up to 3 days after surgery. Epidural analgesia in every combination, with the exception of hydrophilic opioid–alone regimens, provided superior postoperative analgesia compared with intravenous PCA with opioids. It also seemed that CEI provided superior analgesia compared with PCEA and that epidural local anesthetics with or without opioid provided superior analgesia versus  epidural opioid alone.
Although our current study is similar to our previous publication,15 which did include a subgroup analysis showing the superior analgesia of epidural analgesia over intravenous PCA, this study is different because the primary focus was on a comparison of intravenous PCA to PCEA and CEI. Despite the fact that there was overlap in articles assessed between the two studies (35 of 50 articles from the current meta-analysis were used in our previous meta-analysis), this new systematic review contains more clinically relevant information for anesthesiologists because it compares intravenous PCA with both CEI and PCEA (i.e.  , the current study should not be considered a duplicate publication). Many colleagues, both informally and formally,18 mentioned that our initial analysis15 was not clinically meaningful for them because the majority of postoperative systemic opioids were delivered via  intravenous PCA and because there was no differentiation between CEI and PCEA. As such, we decided to undertake a completely new meta-analysis with different inclusion criteria to reflect typical clinical practice.
The results of our meta-analysis corroborate previous systematic reviews of the analgesic efficacy of postoperative epidural analgesia versus  systemic opioids, which include but are not limited to intravenous PCA with opioids.15,16 It may not be surprising that postoperative PCEA and CEI provide significantly superior postoperative analgesia when compared with intravenous PCA with opioids. Unlike that seen with systemic opioids, epidural local anesthetics can block nociceptive input into the central nervous system with the addition of an epidural opioid providing an even greater analgesic effect.20,21 The superior analgesia and physiologic22–24 benefits from epidural analgesia may potentially result in an improvement in perioperative outcomes.25–30 In addition, perioperative epidural analgesia may decrease postoperative morbidity (e.g.  , pulmonary complications, myocardial infarction, gastrointestinal motility) and mortality in high-risk patients, although its effect may not be as apparent for low-risk patients or those undergoing lower-risk procedures.11,31–39 
By allowing individualization of postoperative analgesic requirements, intravenous PCA is considered to be the accepted standard by which opioids are delivered to the hospitalized surgical patient. Intravenous PCA provides significantly superior analgesia compared with conventional “as needed” (intravenous, intramuscular, or subcutaneous) opioid administration.33,40 Similar to that for intravenous PCA and systemic opioids, PCEA may in one sense be considered the accepted standard for delivery of epidural analgesia. In our analysis, PCEA provided significantly superior analgesia compared with intravenous PCA overall, for each postoperative day, and for pain both at rest and with activity. It was interesting to note that CEI provided superior analgesia versus  PCEA; however, this may be possibly related to an increase in dose of local anesthetic administered in the CEI group (i.e.  , subjects receiving PCEA generally use less local anesthetic than those receiving CEI41), which may be reflected in the higher incidence of motor block for those receiving CEI.
Use of a local anesthetic–based epidural regimen seems to provide the best postoperative pain control (table 4). Overall, epidural opioid–only regimens seem to provide superior analgesia compared with intravenous PCA but inferior analgesia compared with local anesthetic–based epidural regimens (i.e.  , VAS values for epidural opioids are intermediate between that for intravenous PCA and local anesthetic–based epidural regimens). However, when analyzed by hydrophilic versus  lipophilic opioids, the VAS pain scores for epidural hydrophilic opioid–only regimens (delivered primarily via  a PCA device) were significantly higher than those for lipophilic opioids and local anesthetic regimens and were for the most part equivalent to those for intravenous PCA. As such, hydrophilic opioid–only epidural solutions should not be routinely administered via  a PCA device for postoperative pain management. In addition, our data also suggest that epidural analgesia would provide superior analgesia compared with intravenous PCA for all types of surgery (table 5). This may be important not only in allowing patients to actively participate in physiotherapy but also in potentially decreasing the incidence of chronic postoperative pain.4 
The overall complication rates reported are similar to those seen in other sources, although the actual incidence in clinical practice may vary depending on the epidural agent used and how the specific complication is defined. The cumulative incidence of nausea–vomiting from epidural analgesia may be as high as 45–80%,42,43 and that for pruritus may be as high as 60%.44 However, some large-scale observational PCEA studies note a lower incidence of nausea–vomiting (3.8–14.8%), pruritus (1.8–16.7%), and motor block (0.1–2%) compared with our findings.45,46 
There are several limitations to this study, some of which pertain specifically with the issue examined, whereas others relate to the general use of meta-analysis. The clinical significance of our findings despite the presence of a statistical difference is unclear (i.e.  , is this a clinically meaningful difference?). We were unable to determine the percentage of patients with moderate–severe pain, the percentage of maximum total pain relief, the sum of the pain intensity difference, or the percentage pain intensity difference47,48 because of the limitations of available data. In addition, attempting to achieve the lowest possible pain score, a worthy objective per se  , may not always be the most desirable or only goal of a postoperative analgesic regimen and must be considered in the overall context of what may be sacrificed (i.e.  , side effects) to achieve this objective. For example, our data suggest that patients receiving CEI have lower pain scores than those receiving PCEA (table 3); however, this superior analgesia may come at a cost (i.e.  , increased nausea–vomiting and motor block; table 6). In addition, the generalizability of our results to the typical clinical population is difficult to assess, in part because of the protocolization present in randomized trials and the rate of failure or dislodgement of postoperative epidural catheters (reported from 6 to 25%49–51), which may limit the analgesic efficacy of epidural analgesia. We also did not weight the quality scoring of the randomized controlled trials used or assess the articles in a blinded fashion because the role of quality assessments in meta-analysis is unclear.52–55 
In addition, that there may be discrepancies between meta-analyses and subsequent large randomized controlled trials.56 This may be related in part to the presence of publication bias where only positive findings are published primarily in English-language journals.57,58 Although we limited our analysis to the English language, only 8 non-English PubMed articles would have qualified for inclusion in our meta-analysis, and the inclusion of these articles (5 studies [n = 395 out of 514 subjects total] of which showed that epidural analgesia produced superior analgesia vs.  intravenous PCA) would not have changed our results. The effect of excluding non-English trials on the results of a meta-analysis is equivocal, with some data suggesting that exclusion of trials published in non-English may actually result in a more conservative estimate of the treatment effect.59 
In summary, we performed a meta-analysis of randomized controlled trials to determine the analgesic efficacy of postoperative epidural analgesia compared with intravenous PCA with opioids. Epidural analgesia provided a statistically and clinically significant improvement in postoperative pain control compared with intravenous PCA with opioids—regardless of analgesic regimen (local anesthetic with or without opioid or opioid alone), type of epidural analgesia (CEI vs.  PCEA), site of surgical incision, or measured pain outcomes (rest or incident pain), with the exception of hydrophilic opioid–only regimens. CEI provided statistically superior (although not necessarily clinically superior) postoperative analgesia versus  PCEA, but with a higher incidence of nausea–vomiting and motor block. Our results suggest that postoperative PCEA and CEI may provide significantly superior analgesia when compared with intravenous PCA, the accepted standard for delivery of postoperative opioids. These analgesic benefits, along with other potential benefits,60–65 should be weighed against the risks66–71 of epidural analgesia when considering the route of delivery for postoperative analgesia, and the balance between these risks and benefits should be determined for each surgical patient.72 When feasible, clinicians may also consider using PCEA with a local anesthetic–based solution over CEI to minimize analgesic-related side effects while providing superior postoperative analgesia compared with intravenous PCA with opioids.
The authors thank the following colleagues for taking the time out of their busy schedules to attempt to review and retrieve their original data for incorporation in this meta-analysis. The authors greatly appreciate their time and effort.
Stephen Barratt, Ph.D., F.A.N.Z.C.A. (Consultant, Department of Anesthesia and Pain Management, Royal North Shore Hospital, St. Leonards, Australia); Honorio Benzon, M.D. (Professor of Anesthesiology, Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois); Xavier Capdevila, M.D., Ph.D. (Professor, Department of Anesthesiology, Lapeyronie University Hospital, Montpellier, France); Phoon P. Chen, M.D., F.H.K.A.M. (Honorary Associate Professor, Department Anesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, SAR of China); David Cooper, F.R.C.A. (Consultant Anesthetist, James Cook University Hospital, Middlesbrough, United Kingdom); Rob Dyer, F.C.A. (SA) (Senior Specialist, Department of Anesthesia, Groote Schuur Hospital, Cape Town, South Africa); Charles Fisher, M.D., M.H.Sc., F.R.C.S.C. (Department of Orthopaedics, Vancouver Hospital and Health Sciences Centre, Vancouver, Canada); Per Flisberg, M.D., Ph.D. (Consultant, Department of Anesthesia and Pain Medicine, Royal Perth Hospital, Perth, Australia); Johan Lundberg, M.D., Ph.D. (Adjunct Professor of Anesthesiology, Dartmouth Medical School, Hanover, New Hampshire); Edward Norris, M.D. (Associate Professor, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, Maryland); Mark Priestley, M.B.B.S., F.A.N.Z.C.A. (Consultant, Department of Anesthesia, Westmead Hospital, Westmead, Australia); Yehuda (Udi) Shavit (Professor, Department of Psychology, Hebrew University, Jerusalem, Israel); Eugene Viscusi, M.D. (Associate Professor, Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania); and Avi Weinbroum, M.D. (Director, Post-Anesthesia Care Unit and Animal Research Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel).
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Wu CL, Hurley RW, Anderson GF, Herbert R, Rowlingson AJ, Fleisher LA: The effect of perioperative epidural analgesia on patient mortality and morbidity in the Medicare population. Reg Anesth Pain Med 2004; 29:525–33Wu, CL Hurley, RW Anderson, GF Herbert, R Rowlingson, AJ Fleisher, LA
Liu SS: Anesthesia and analgesia for colon surgery. Reg Anesth Pain Med 2004; 29:52–7Liu, SS
Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: A meta-analysis. Anesthesiology 2004; 101:153–61Liu, SS Block, BM Wu, CL
Wu CL, Anderson GF, Herbert R, Lietman SA, Fleisher LA: Effect of postoperative epidural analgesia on morbidity and mortality after total hip replacement surgery in Medicare patients. Reg Anesth Pain Med 2003; 28:271–8Wu, CL Anderson, GF Herbert, R Lietman, SA Fleisher, LA
Liu SS: Bank robbers and outcomes research. Reg Anesth Pain Med 2003; 28:262–4Liu, SS
Neal JM, Wilcox RT, Allen HW, Low DE: Near-total esophagectomy: the influence of standardized multimodal management and intraoperative fluid restriction. Reg Anesth Pain Med 2003; 28:328–34Neal, JM Wilcox, RT Allen, HW Low, DE
Walder B, Schafer M, Henzi I, Tramer MR: Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain: A quantitative systematic review. Acta Anaesthesiol Scand 2001; 45:795–804Walder, B Schafer, M Henzi, I Tramer, MR
Assad SA, Isaacson SA, Wu CL: An update on patient-controlled epidural analgesia. Techniques Reg Anesth Pain Med 2003; 7:127–32Assad, SA Isaacson, SA Wu, CL
Borgeat A, Ekatodramis G, Schenker CA: Postoperative nausea and vomiting in regional anesthesia: A review. Anesthesiology 2003; 98:530–47Borgeat, A Ekatodramis, G Schenker, CA
Gedney JA, Liu EH: Side-effects of epidural infusions of opioid bupivacaine mixtures. Anaesthesia 1998; 53:1148–55Gedney, JA Liu, EH
Kjellberg F, Tramer MR: Pharmacological control of opioid-induced pruritus: A quantitative systematic review of randomized trials. Eur J Anaesthesiol 2001; 18:346–57Kjellberg, F Tramer, MR
Wigfull J, Welchew E: Survey of 1057 patients receiving postoperative patient-controlled epidural analgesia. Anaesthesia 2001; 56:70–5Wigfull, J Welchew, E
Liu SS, Allen HW, Olsson GL: Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital wards: Prospective experience with 1,030 surgical patients. Anesthesiology 1998; 88:688–95Liu, SS Allen, HW Olsson, GL
Farrar JT, Portenoy RK, Berline JA, Kinman JL, Strom BL: Defining the clinically important difference in pain outcome measures. Pain 2000; 88:287–94Farrar, JT Portenoy, RK Berline, JA Kinman, JL Strom, BL
Farrar JT, Berlin JA, Strom BL: Clinically important changes in acute pain outcome measures: A validation study. J Pain Symptom Manage 2003; 25:406–11Farrar, JT Berlin, JA Strom, BL
Scott DA, Beilby DS, McClymont C: Postoperative analgesia using epidural infusions of fentanyl with bupivacaine: A prospective analysis of 1,014 patients. Anesthesiology 1995; 83:727–37Scott, DA Beilby, DS McClymont, C
Ready LB: Acute pain: Lessons learned from 25,000 patients. Reg Anesth Pain Med 1999; 24:499–505Ready, LB
de Leon-Casasola OA, Parker B, Lema MJ, Harrison P, Massey J: Postoperative epidural bupivacaine–morphine therapy: Experience with 4,227 surgical cancer patients. Anesthesiology 1994; 81:368–75de Leon-Casasola, OA Parker, B Lema, MJ Harrison, P Massey, J
Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP: Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 1998; 352:609–13Moher, D Pham, B Jones, A Cook, DJ Jadad, AR Moher, M Tugwell, P Klassen, TP
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17:1–12Jadad, AR Moore, RA Carroll, D Jenkinson, C Reynolds, DJ Gavaghan, DJ McQuay, HJ
Balk EM, Bonis PA, Moskowitz H, Schmid CH, Ioannidis JP, Wang C, Lau J: Correlation of quality measures with estimates of treatment effect in meta-analyses of randomized controlled trials. JAMA 2002; 287:2973–82Balk, EM Bonis, PA Moskowitz, H Schmid, CH Ioannidis, JP Wang, C Lau, J
Clark HD, Wells GA, Huet C, McAlister FA, Salmi LR, Fergusson D, Laupacis A: Assessing the quality of randomized trials: Reliability of the Jadad scale. Control Clin Trials 1999; 20:448–52Clark, HD Wells, GA Huet, C McAlister, FA Salmi, LR Fergusson, D Laupacis, A
LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F: Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med 1997; 337:536–42LeLorier, J Gregoire, G Benhaddad, A Lapierre, J Derderian, F
Moher D, Pham B, Lawson ML, Klassen TP: The inclusion of reports of randomised trials published in languages other than English in systematic reviews. Health Technol Assess 2003; 7:1–90Moher, D Pham, B Lawson, ML Klassen, TP
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Juni P, Holenstein F, Sterne J, Barlett C, Egger M: Direction and impact of language bias in meta-analyses of controlled trials: Empirical study. Int J Epidemiol 2002; 31:115–23Juni, P Holenstein, F Sterne, J Barlett, C Egger, M
Cassady Jr, JF Lederhaas G, Cancel DD, Cummings RJ, Loveless EA: A randomized comparison of the effects of continuous thoracic epidural analgesia and intravenous patient-controlled analgesia after posterior spinal fusion in adolescents. Reg Anesth Pain Med 2000; 25:246–53Cassady, JF Lederhaas, G Cancel, DD Cummings, RJ Loveless, EA
Katz J, Cohen L, Schmid R, Chan VW, Wowk A: Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: Implications for preemptive analgesia and the prevention of central sensitization. Anesthesiology 2003; 98:1449–60Katz, J Cohen, L Schmid, R Chan, VW Wowk, A
Matot I, Oppenheim-Eden A, Ratrot R, Baranova J, Davidson E, Eylon S, Peyser A, Liebergall M: Preoperative cardiac events in elderly patients with hip fracture randomized to epidural or conventional analgesia. Anesthesiology 2003; 98:156–63Matot, I Oppenheim-Eden, A Ratrot, R Baranova, J Davidson, E Eylon, S Peyser, A Liebergall, M
Buggy DJ, Doherty WL, Hart EM, Pallett EJ: Postoperative wound oxygen tension with epidural or intravenous analgesia: A prospective, randomized, single-blind clinical trial. Anesthesiology 2002; 97:952–8Buggy, DJ Doherty, WL Hart, EM Pallett, EJ
Mann C, Pouzeratte Y, Boccara G, Peccoux C, Vergne C, Brunat G, Domergue J, Millat B, Colson P: Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000; 92:433–41Mann, C Pouzeratte, Y Boccara, G Peccoux, C Vergne, C Brunat, G Domergue, J Millat, B Colson, P
Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d’Athis F: Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91:8–15Capdevila, X Barthelet, Y Biboulet, P Ryckwaert, Y Rubenovitch, J d’Athis, F
Horlocker TT, Wedel DJ, Benzon H, Brown DL, Enneking FK, Heit JA, Mulroy MF, Rosenquist RW, Rowlingson J, Tryba M, Yuan CS: Regional anesthesia in the anticoagulated patient: Defining the risks. Reg Anesth Pain Med 2003; 28:172–97Horlocker, TT Wedel, DJ Benzon, H Brown, DL Enneking, FK Heit, JA Mulroy, MF Rosenquist, RW Rowlingson, J Tryba, M Yuan, CS
Horlocker TT, Wedel DJ: Neurologic complications of spinal and epidural anesthesia. Reg Anesth Pain Med 2000; 25:83–98Horlocker, TT Wedel, DJ
Mulroy MF: Systemic toxicity and cardiotoxicity from local anesthetics: Incidence and preventive measures. Reg Anesth Pain Med 2002; 27:556–61Mulroy, MF
Moen V, Dahlgren N, Irestedt L: Severe neurological complications after central neuraxial blockades in Sweden 1990–1999. Anesthesiology 2004; 101:950–9Moen, V Dahlgren, N Irestedt, L
Wang LP, Hauerberg J, Schmidt JF: Incidence of spinal epidural abscess after epidural analgesia: A national 1-year survey. Anesthesiology 1999; 91:1928–36Wang, LP Hauerberg, J Schmidt, JF
Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier FJ, Bouaziz H, Samii K, Mercier F: Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service. Anesthesiology 2002; 97:1274–80Auroy, Y Benhamou, D Bargues, L Ecoffey, C Falissard, B Mercier, FJ Bouaziz, H Samii, K Mercier, F
Bergqvist D, Wu CL, Neal JM: Anticoagulation and neuraxial regional anesthesia: Perspectives. Reg Anesth Pain Med 2003; 28:163–5Bergqvist, D Wu, CL Neal, JM
Appendix: Included Articles
1. Allaire PH, Messick JM Jr, Oesterling JE, Byer DE, Myers RP, Lieber MM, Chantigian RC, Welna JO, Patterson DE, Blute ML: A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy. Mayo Clin Proc 1992; 67:1031–41
2. Barratt SM, Smith RC, Kee AJ, Mather LE, Cousins MJ: Multimodal analgesia and intravenous nutrition preserves total body protein following major upper gastrointestinal surgery. Reg Anesth Pain Med 2002; 27:15–22
3. Baxter AD, Laganiere S, Samson B, Stewart J, Hull K, Goernert L: A comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy analgesia. Can J Anaesth 1994; 41:184–91
4. Beilin B, Shavit Y, Trabekin E, Mordashev B, Mayburd E, Zeidel A, Bessler H: The effects of postoperative pain management on immune response to surgery. Anesth Analg 2003; 97:822–7
5. Benzon HT, Wong HY, Belavic AM Jr, Goodman I, Mitchell D, Lefheit T, Locicero J: A randomized double-blind comparison of epidural fentanyl infusion versus  patient-controlled analgesia with morphine for postthoracotomy pain. Anesth Analg 1993; 76:316–22
6. Bois S, Couture P, Boudreault D, Lacombe P, Fugere F, Girard D, Nadeau N: Epidural analgesia and intravenous patient-controlled analgesia result in similar rates of postoperative myocardial ischemia after aortic surgery. Anesth Analg 1997; 85:1233–9
7. Boisseau N, Rabary O, Padovani B, Staccini P, Mouroux J, Grimaud D, Raucoules-Aime M: Improvement of “dynamic analgesia” does not decrease atelectasis after thoracotomy. Br J Anaesth 2001; 87:564–9
8. Boylan JF, Katz J, Kavanagh BP, Klinck JR, Cheng DC, DeMajo WC, Walker PM, Johnston KW, Sandler AN: Epidural bupivacaine–morphine analgesia versus  patient-controlled analgesia following abdominal aortic surgery: Analgesic, respiratory, and myocardial effects. Anesthesiology 1998; 89:585–93
9. Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d’Athis F: Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91:8–15
10. Carli F, Trudel JL, Belliveau P: The effect of intraoperative thoracic epidural anesthesia and postoperative analgesia on bowel function after colorectal surgery: A prospective, randomized trial. Dis Colon Rectum 2001; 44:1083–9
11. Carli F, Mayo N, Klubien K, Schricker T, Trudel J, Belliveau P: Epidural analgesia enhances functional exercise capacity and health-related quality of life after colonic surgery: Results of a randomized trial. Anesthesiology 2002; 97:540–9
12. Chen PP, Cheam EW, Ma M, Lam KK, Ngan Kee WD, Gin T: Patient-controlled pethidine after major upper abdominal surgery: Comparison of the epidural and intravenous routes. Anesthesia 2001; 56:1106–12
13. Cohen BE, Hartman MB, Wade JT, Miller JS, Gilbert R, Chapman TM: Postoperative pain control after lumbar spine fusion: Patient-controlled analgesia versus  continuous epidural analgesia. Spine 1997; 22:1892–6
14. Cooper DW, Saleh U, Taylor M, Whyte S, Ryall D, Kokri MS, Desira WR, Day H, McArthur E: Patient-controlled analgesia: Epidural fentanyl and i.v. morphine compared after caesarean section. Br J Anaesth 1999; 82:366–70
15. Cooper DW, Ryall DM, Desira WR: Extradural fentanyl for postoperative analgesia: Predominant spinal or systemic action? Br J Anaesth 1995; 74:184–7
16. Correll DJ, Viscusi ER, Grunwald Z, Moore JH Jr: Epidural analgesia compared with intravenous morphine patient-controlled analgesia: Postoperative outcome measures after mastectomy with immediate TRAM flap breast reconstruction. Reg Anesth Pain Med 2001; 26:444–9
17. Flisberg P, Tornebrandt K, Walther B, Lundberg J: Pain relief after esophagectomy: Thoracic epidural analgesia is better than parenteral opioids. J Cardiothorac Vasc Anesth 2001; 15:282–7
18. George KA, Wright PM, Chisakuta AM, Rao NV: Thoracic epidural analgesia compared with patient controlled intravenous morphine after upper abdominal surgery. Acta Anaesthesiol Scand 1994; 38:808–12
19. Jayr C, Beaussier M, Gustafsson U, Leteurnier Y, Nathan N, Plaud B, Tran G, Varlet C, Marty J: Continuous epidural infusion of ropivacaine for postoperative analgesia after major abdominal surgery: Comparative study with i.v. PCA morphine. Br J Anaesth 1998; 81:887–92
20. Joshi GP, McCarroll SM, O’Rourke K: Postoperative analgesia after lumbar laminectomy: Epidural fentanyl infusion versus  patient-controlled intravenous morphine. Anesth Analg 1995; 80:511–4
21. Kampe S, Randebrock G, Kiencke P, Hunseler U, Cranfield K, Konig DP, Diefenbach C: Comparison of continuous epidural infusion of ropivacaine and sufentanil with intravenous patient-controlled analgesia after total hip replacement. Anesthesia 2001; 56:1189–93
22. Klasen JA, Opitz SA, Melzer C, Thiel A, Hempelmann G: Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty. Acta Anaesthesiol Scand 1999; 43:1021–6
23. Licker M, Suter PM, Krauer F, Rifat NK: Metabolic response to lower abdominal surgery: Analgesia by epidural blockade compared with intravenous opiate infusion. Eur J Anaesthesiol 1994; 11:193–9
24. Liu S, Carpenter RL, Mulroy MF, Weissman RM, McGill TJ, Rupp SM, Allen HW: Intravenous versus  epidural administration of hydromorphone: Effects on analgesia and recovery after radical retropubic prostatectomy. Anesthesiology 1995; 82:682–8
25. Liu SS, Carpenter RL, Mackey DC, Thirlby RC, Rupp SM, Shine TS, Feinglass NG, Metzger PP, Fulmer JT, Smith SL: Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology 1995; 83:757–65
26. Madej TH, Wheatley RG, Jackson IJ, Hunter D: Hypoxaemia and pain relief after lower abdominal surgery: comparison of extradural and patient-controlled analgesia. Br J Anaesth 1992; 69:554–7
27. Mann C, Pouzeratte Y, Boccara G, Peccoux C, Vergne C, Brunat G, Domergue J, Millat B, Colson P: Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000; 92:433–41
28. Menigaux C, Guignard B, Fletcher D, Sessler DI, Levron JC, Chauvin M: More epidural than intravenous sufentanil is required to provide comparable postoperative pain relief. Anesth Analg 2001; 93:472–6
29. Moon MR, Luchette FA, Gibson SW, Crews J, Sudarshan G, Hurst JM, Davis K Jr, Johannigman JA, Frame SB, Fischer JE: Prospective, randomized comparison of epidural versus  parenteral opioid analgesia in thoracic trauma. Ann Surg 1999; 229:684–91
30. Motamed C, Spencer A, Farhat F, Bourgain JL, Lasser P, Jayr C: Postoperative hypoxaemia: Continuous extradural infusion of bupivacaine and morphine versus  patient-controlled analgesia with intravenous morphine. Br J Anaesth 1998; 80:742–7
31. Nendick M: Patient satisfaction with postoperative analgesia. Nurs Stand 2000; 14:32–7
32. Parker RK, White PF: Epidural patient-controlled analgesia: An alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery. Anesth Analg 1992; 75:245–51
33. Paulsen EK, Porter MG, Helmer SD, Linhardt PW, Kliewer ML: Thoracic epidural versus  patient-controlled analgesia in elective bowel resections. Am J Surg 2001; 182:570–7
34. Priestley MC, Cope L, Halliwell R, Gibson P, Chard RB, Skinner M, Klineberg PL: Thoracic epidural anesthesia for cardiac surgery: The effects on tracheal intubation time and length of hospital stay. Anesth Analg 2002; 94:275–82
35. Rigg JR, Jamrozik K, Myles PS, Silbert BS, Peyton PJ, Parsons RW, Collins KS; MASTER Anaethesia Trial Study Group: Epidural anesthesia and analgesia and outcome of major surgery: A randomized trial. Lancet 2002; 359:1276–82
36. Schricker T, Wykes L, Eberhart L, Lattermann R, Mazza L, Carli F: The anabolic effect of epidural blockade requires energy and substrate supply. Anesthesiology 2002; 97:943–51
37. Schumann R, Shikora S, Weiss JM, Wurm H, Strassels S, Carr DB: A comparison of multimodal perioperative analgesia to epidural pain management after gastric bypass surgery. Anesth Analg 2003; 96:469–74
38. Senagore AJ, Delaney CP, Mekhail N, Dugan A, Fazio VW: Randomized clinical trial comparing epidural anesthesia and patient-controlled analgesia after laparoscopic segmental colectomy. Br J Surg 2003; 90:1195–9
39. Senturk M, Ozcan PE, Talu GK, Kiyan E, Camci E, Ozyalcin S, Dilege S, Pembeci K: The effects of three different analgesia techniques on long-term postthoracotomy pain. Anesth Analg 2002; 94:11–5
40. Sinatra RS, Sevarino FB, Paige D: Patient-controlled analgesia with sufentanil: A comparison of two different methods of administration. J Clin Anesth 1996; 8:123–9
41. Singelyn FJ, Deyaert M, Joris D, Pendeville E, Gouverneur JM: Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty. Anesth Analg 1998; 87:88–92
42. Slinger P, Shennib H, Wilson S: Postthoracotomy pulmonary function: A comparison of epidural versus  intravenous meperidine infusions. J Cardiothorac Vasc Anesth 1995; 9:128–34
43. Steinberg RB, Liu SS, Wu CL, Mackey DC, Grass JA, Ahlen K, Jeppsson L: Comparison of ropivacaine-fentanyl patient-controlled epidural analgesia with morphine intravenous patient-controlled analgesia for perioperative analgesia and recovery after open colon surgery. J Clin Anesth 2002; 14:571–7
44. Tavernier B, Tellez J, Triboulet JP: Thoracic epidural bupivacaine combined with opioid for esophagectomy. Surgery 1998; 123:113–4
45. Tsui SL, Lee DK, Ng KF, Chan TY, Chan WS, Lo JW: Epidural infusion of bupivacaine 0.0625% plus fentanyl 3.3 micrograms/ml provides better postoperative analgesia than patient-controlled analgesia with intravenous morphine after gynaecological laparotomy. Anaesth Intensive Care 1997; 25:476–81
46. Volk T, Schenk M, Voigt K, Tohtz S, Putzier M, Kox WJ: Postoperative epidural anesthesia preserves lymphocyte, but not monocyte, immune function after major spine surgery. Anesth Analg 2004; 98:1086–92
47. Weinbroum AA, Bender B, Nirkin A, Chazan S, Meller I, Kollender Y: Dextromethorphan-associated epidural patient-controlled analgesia provides better pain- and analgesics-sparing effects than dextromethorphan-associated intravenous patient-controlled analgesia after bone-malignancy resection: A randomized, placebo-controlled, double-blinded study. Anesth Analg 2004; 98:714–22
48. Welchew EA, Breen DP: Patient-controlled on-demand epidural fentanyl: A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. Anesthesia 1991; 46:438–41
49. Wheatley RG, Somerville ID, Sapsford DJ, Jones JG: Postoperative hypoxaemia: Comparison of extradural, intramuscular and patient-controlled opioid analgesia. Br J Anaesth 1990; 64:267–75
50. Wulf H, Biscoping J, Beland B, Bachmann-Mennenga B, Motsch J: Ropivacaine epidural anesthesia and analgesia versus  general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group. Anesth Analg 1999; 89:111–6
Table 1. Characteristics of Included Studies 
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Table 1. Characteristics of Included Studies 
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Table 2. Aggregate VAS Pain Data 
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Table 2. Aggregate VAS Pain Data 
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Table 3. PCEA VAS Pain Data 
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Table 3. PCEA VAS Pain Data 
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Table 4. Epidural Analgesic Data 
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Table 4. Epidural Analgesic Data 
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Table 5. Analgesia by Region of Surgery 
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Table 5. Analgesia by Region of Surgery 
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Table 6. Complication Rates 
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Table 6. Complication Rates 
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