Epidural analgesia versus patient-controlled intravenous analgesia for pain following intra-abdominal surgery in adults.

BACKGROUND: Intravenous patient-controlled analgesia (IVPCA) with opioids and epidural analgesia (EA) using either continuous epidural administration (CEA) or patient-controlled (PCEA) techniques are popular approaches for analgesia following intra-abdominal surgery. Despite several attempts to compare the risks and benefits, the optimal form of analgesia for these procedures remains the subject of debate.

OBJECTIVES: The objective of this review was to update and expand a previously published Cochrane Review on IVPCA versus CEA for pain after intra-abdominal surgery with the addition of the comparator PCEA. We have compared both forms of EA to IVPCA. Where appropriate we have performed subgroup analysis for CEA versus PCEA.

SEARCH METHODS: We searched the following electronic databases for relevant studies: Cochrane Central Register of Controlled Trials (CENTRAL) (2017; Issue 8), MEDLINE (OvidSP) (1966 to September 2017), and Embase (OvidSP) (1988 to September 2017) using a combination of MeSH and text words. We searched the following trial registries: Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, and the EU Clinical Trials Register in September 2017, together with reference checking and citation searching to identify additional studies.We included only randomized controlled trials and used no language restrictions.

SELECTION CRITERIA: We included all parallel and cross-over randomized controlled trials (RCTs) comparing CEA or PCEA (or both) with IVPCA for postoperative pain relief in adults following intra-abdominal surgery.

DATA COLLECTION AND ANALYSIS: Two review authors (JS and EY) independently identified studies for eligibility and performed data extraction using a data extraction form. In cases of disagreement (three occasions) a third review author (MB) was consulted. We appraised each included study to assess the risk of bias as outlined in Section 8.5 of the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE to assess the quality of the evidence.

MAIN RESULTS: We included 32 studies (1716 participants) in our review. There are 10 studies awaiting classification and one ongoing study. A total of 869 participants (51%) received EA and 847 (49%) received IVPCA. The EA trials included 16 trials with CEA (418 participants) and 16 trials with PCEA (451 participants). The studies included a broad range of surgical procedures (including hysterectomies, radical prostatectomies, Caesarean sections, colorectal and upper gastrointestinal procedures), a wide range of adult ages, and were performed in several different countries.Our pooled analyses suggested a benefit with regard to pain scores (using a visual analogue scale between 0 and 100) in favour of EA techniques at rest. The mean pain reduction at rest from waking to six hours after operation was 5.7 points (95% confidence interval (CI) 1.9 to 9.5; 7 trials, 384 participants; moderate-quality evidence). From seven to 24 hours, the mean pain reduction was 9.0 points (95% CI 4.6 to 13.4; 11 trials, 558 participants; moderate-quality evidence). From 24 hours the mean pain reduction was 5.1 points (95% CI 0.9 to 9.4; 7 trials, 393 participants; moderate-quality evidence). Due to high statistical heterogeneity, no pooled analysis was possible for the estimation of pain on movement at any time. Two single studies (one using CEA and one PCEA) reported lower pain scores with EA compared to IVPCA at 0 to 6 hours and 7 to 24 hours. At > 24 hours the results from 2 studies (both CEA) were conflicting.We found no difference in mortality between EA and IVPCA, although the only deaths reported were in the EA group (5/287, 1.7%). The risk ratio (RR) of death with EA compared to using IVPCA was 3.37 (95% CI 0.72 to 15.88; 9 trials, 560 participants; low-quality evidence).A single study suggested that the use of EA may result in fewer episodes of respiratory depression, with an RR of 0.47 (95% CI 0.04 to 5.69; 1 trial; low-quality evidence). The successful placement of an epidural catheter can be technically challenging. The improvements in pain scores above were accompanied by an increase in the risk of failure of the analgesic technique with EA (RR 2.48, 95% CI 1.13 to 5.45; 10 trials, 678 participants; moderate-quality evidence); the occurrence of pruritus (RR 2.36, 95% CI 1.67 to 3.35; 8 trials, 492 participants; moderate-quality evidence); and episodes of hypotension requiring intervention (RR 7.13, 95% CI 2.87 to 17.75; 6 trials, 479 participants; moderate-quality evidence). There was no clear evidence of an advantage of one technique over another for other adverse effects considered in this review (Venous thromboembolism with EA (RR 0.32, 95% CI 0.03 to 2.95; 2 trials, 101 participants; low-quality evidence); nausea and vomiting (RR 0.94, 95% CI 0.69 to 1.27; 10 trials, 645 participants; moderate-quality evidence); sedation requiring intervention (RR 0.87, 95% CI 0.40 to 1.87; 4 trials, 223 participants; moderate-quality evidence); or episodes of desaturation to less than 90% (RR 1.29, 95% CI 0.71 to 2.37; 5 trials, 328 participants; moderate-quality evidence)).

AUTHORS' CONCLUSIONS: The additional pain reduction at rest associated with the use of EA rather than IVPCA is modest and unlikely to be clinically important. Single-trial estimates provide low-quality evidence that there may be an additional reduction in pain on movement, which is clinically important. Any improvement needs to be interpreted with the understanding that the use of EA is also associated with an increased chance of failure to successfully institute analgesia, and an increased likelihood of episodes of hypotension requiring intervention and pruritus. We have rated the evidence as of moderate quality given study limitations in most of the contributing studies. Further large RCTs are required to determine the ideal analgesic technique. The 10 studies awaiting classification may alter the conclusions of the review once assessed.