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To compare outcomes following open liver resection (OLR) between patients receiving thoracic epidural (EP) versus abdominal wound catheters plus patient-controlled analgesia (AWC-PCA).Patients were randomized 1:1 to either EP or AWC-PCA within an enhanced recovery protocol. Primary outcome was length of stay (LOS), other variables included functional recovery, pain scores, peak flow, vasopressor and fluid requirements, and postoperative complications.Between April 2015 and November 2017, 83 patients were randomized to EP (n = 41) or AWC-PCA (n = 42). Baseline demographics were comparable. No difference was noted in LOS (EP 6 d (3–27) vs AWC-PCA 6 d (3–66), P = 0.886). Treatment failure was 20% in the EP group versus 7% in the AWC-PCA (P = 0.09). Preoperative anesthetic time was shorter in the AWC-PCA group, 49 minutes versus 62 minutes (P = 0.003). EP patients required more vasopressor support immediately postoperatively on day 0 (14% vs 54%, P = <0.001) and day 1 (5% vs 23%, P = 0.021). Pain scores were greater on day 0, afternoon of day 1 and morning of day 2 in the AWC-PCA group however were regarded as low at all time points. No other significant differences were noted in IV fluid requirements, nausea/sedation scores, days to open bowels, length of HDU, and postoperative complications.AWC-PCA was associated with reduced treatment failure and a reduced vasopressor requirement than EP up to 2 days postoperatively. While the use of AWC-PCA did not translate into a shorter LOS in this study, it simplified patient management after OLR. EP cannot be routinely recommended following open liver resections.