The Effects of Local Anaesthetic Infiltration via Wound Catheters versus Epidural Analgesia on Recovery Following Open Liver Resection

Introduction Epidural analgesia provides satisfactory pain relief but is not without unwanted side effects or a significant failure rate. New multi-modal methods of delivering postoperative analgesia are being developed which aim to minimize side effects and enhance recovery. The aim of this thesis was to compare recovery following open liver resection (OLR) between patients receiving thoracic epidural (EP) or abdominal wound catheters plus patient-controlled analgesia (AWC-PCA). Method In order to address the aim of this thesis the following studies were developed: 1. A systematic review of current modalities used for post-operative analgesia and current evidence for ERAS protocols in liver surgery. 2. A systematic review and meta-analysis comparing outcomes between EP and AWC following open liver resection. This was performed according to PRISMA guidelines. 3. An open-label randomized controlled trial allocating participants 1:1 to receive either EP or AWC-PCA within an enhanced recovery protocol. Primary outcome was length of stay (LOS). Secondary outcomes included functional recovery, pain scores, peak flow, vasopressor, fluid requirements and postoperative complications. 4. An assessment of the impact the two methods of analgesia have on the systemic inflammatory response by analysing and comparing cytokine levels at baseline (Day 0), Day 1 and Day 3 post-surgery in patients enrolled in the randomized controlled trial. Results For parts 1 & 2, five studies were included in the analysis. Pain scores were significantly better in the EP group on postoperative day 1 but comparable thereafter. The complication rate was worse in the EP group. Length of stay was comparable as were the other secondary outcomes. The included studies were of generally poor quality with only 2 randomised controlled trials specific to liver resection published. For part 3, 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 days (3-27) vs. AWC-PCA 6 days (3-66), p=0.886). Treatment failure was 20% in the EP group vs. 7% in the AWC-PCA (p=0.09). Preoperative anaesthetic time was shorter in the AWC-PCA group, 49 min vs. 62 min (p=0.003). EP patients required more vasopressor support immediately postoperatively on day 0 (14% vs 54%, p=<0.001) and day 1 (5% v 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. For part 4, thirty patients were recruited into the cytokine analysis section of this study, 17 in the AWC-PCA group and 13 in the EP group. Patients in the EP arm were more likely to be ASA II and have a more extensive liver resection. Interleukin-9 and MIP-1b levels were significantly lower with time in the AWC-PCA arm. There were no other differences in cytokine levels between the two groups. Conclusion AWC-PCA was associated with reduced treatment failure and a reduced vasopressor requirement than EP up to two days post-operatively. Whilst the use of AWC-PCA did not translate into a shorter LOS in this study it simplified patient management after OLR. The inflammatory response was comparable. AWC-PCA was not inferior to EP when used in patients undergoing open liver resection. EP cannot be routinely recommended following open liver resections based on the evidence gathered throughout this study.