Michael J. Hughes

Enhanced recovery following liver surgery: a systematic review and meta-analysis

BACKGROUND Enhanced recovery after surgery (ERAS) programmes aim to improve postoperative outcomes. They are being utilized increasingly in hepatic surgery. This review aims to evaluate the impact of ERAS programmes on outcomes following liver surgery. METHODS EMBASE, MEDLINE, PubMed and the Cochrane Database were searched for trials comparing outcomes in patients undergoing liver surgery utilizing ERAS principles with those in patients receiving conventional care. The primary outcome was occurrence of postoperative complications within 30 days. Secondary outcomes included length of stay (LoS), functional recovery and adherence to ERAS protocols. RESULTS Nine articles were included in the review, of which two were randomized controlled trials (RCTs). Overall complication rates were 25.0% (range: 11.5-46.4%) in ERAS patients, and 31.0% (range: 11.8-46.2%) in conventional care patients. Significantly reduced overall complication rates following ERAS care were demonstrated by a meta-analysis of the data reported in the two RCTs (odds ratio: 0.49, 95% confidence interval 0.28-0.84; P = 0.01) The median LoS reported by the studies was 5.0 days (range: 2.5-7.0 days) in ERAS patients, and 7.5 days (range: 3.0-11.0 days) in non-ERAS patients. Recovery milestones, when reported, were improved following ERAS care. CONCLUSIONS The adoption of ERAS protocols improves morbidity and LoS following liver surgery. Future ERAS programmes should accommodate the unique requirements of liver surgery in order to optimize postoperative outcomes.

CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients with acute liver injury. CSF1 might be developed as a therapeutic agent to restore innate immune function after liver injury.

Analgesia after open abdominal surgery in the setting of enhanced recovery surgery: a systematic review and meta-analysis.

IMPORTANCE The optimal analgesic technique following open abdominal surgery within an enhanced recovery protocol remains controversial. Thoracic epidural is often recommended; however, its role is increasingly being challenged and alternative techniques are being suggested as suitable replacements. OBJECTIVE To determine by meta-analysis whether epidurals are superior to alternative analgesic techniques following open abdominal surgery within an enhanced recovery setting in terms of postoperative morbidity and other markers of recovery. DATA SOURCES A literature search was performed of EMBASE, Medline, PubMed, and the Cochrane databases from 1966 through May 2013. STUDY SELECTION All randomized clinical trials comparing epidurals with an alternative analgesic technique following open abdominal surgery within an enhanced recovery protocol were included. DATA EXTRACTION AND SYNTHESIS All studies were assessed by 2 independent reviewers. Study quality was assessed using the Cochrane bias assessment tool and the Jadad and Chalmers modified bias risk assessment tools. Dichotomous data were analyzed by random or fixed-effects odds ratios. Qualitative analysis was performed where appropriate. RESULTS Seven trials with a total of 378 patients were identified. No significant difference in complication rate was detected between epidurals and alternative analgesic methods (odds ratio, 1.14; 95% CI, 0.49-2.64; P = .76). Subgroup analysis showed fewer complications in the patient-controlled analgesia group compared with epidural analgesia (odds ratio, 1.97; 95% CI, 1.10-3.53; P = .02). Following qualitative assessment, epidural analgesia was associated with faster return of gut function and reduced pain scores; however, no difference was observed in length of stay. CONCLUSIONS AND RELEVANCE Epidurals may be associated with superior pain control but this does not translate into improved recovery or reduced morbidity when compared with alternative analgesic techniques when used within an enhanced recovery protocol.

Randomized clinical trial of perioperative nerve block and continuous local anaesthetic infiltration via wound catheter versus epidural analgesia in open liver resection (LIVER 2 trial)

Analgesia after liver surgery remains controversial. A previous randomized trial of continuous wound infiltration (CWI) versus thoracic epidural analgesia (TEA) after liver surgery (LIVER trial) showed a faster recovery time in the wound infiltration group but better early postoperative pain scores in the TEA group. High‐level evidence is, however, limited and opinion remains divided. The aim was to determine whether there is a difference in functional recovery time between patients having CWI plus abdominal nerve blocks versus TEA after liver resection.

Central venous pressure and liver resection: a systematic review and meta analysis

BACKGROUND A liver resection under low central venous pressure (CVP) has become standard practice; however, the benefits beyond a reduction in blood loss are not well reported. Moreover, the precise method to achieve CVP reduction has not been established. A systematic review and meta-analysis of randomized controlled trials (RTCs) was performed to assess the effects of CVP on clinical outcome and to identify the optimum method of CVP reduction. METHODS EMBASE, Medline, PubMed and the Cochrane database were searched for trials comparing low CVP surgery with controls. The primary outcome was post-operative complications within 30 days. Secondary outcomes included estimated blood loss (EBL), blood transfusion rates and length of stay (LOS). Sub-group analysis was performed to assess the CVP reduction method on the outcome. RESULTS Eight trials were identified. No difference was observed in the morbidity rate between the high CVP and control groups [odds ratio (OR) = 0.96 (95% confidence interval (CI) 0.66, 1.40) P = 0.84, I(2) = 0%]. EBL [weighted mean difference (WMD) = -308.63 ml (95% CI -474.67, -142.58) P = < 0.001, I(2) = 73%] and blood transfusion rates [OR 0.65 (95% CI 0.44, 0.97) P = 0.040, I(2) = 37%] were significantly lower in the low CVP groups. Neither anaesthetic nor surgical methods of CVP reduction were associated with a reduced post-operative morbidity. CONCLUSION Low CVP surgery is associated with a reduction in EBL; however, this does not translate into an improvement in post-operative morbidity. The optimum method of CVP reduction has not been identified.

Post-Operative Antibiotics after Appendectomy and Post-Operative Abscess Development: A Retrospective Analysis

BACKGROUND Appendectomy is one of the most common emergency operations. Prophylaxis against infective complications involves post-operative antibiotics. There is no consensus as to the optimum antibiotic regimen. This study aimed to assess the relation between the duration of the post-operative antibiotic administration and intra-abdominal infections (IAIs). PATIENTS AND METHODS All patients who underwent appendectomy between September 1, 2009, and August 31, 2010, were identified. The appearance of the appendix at operation, post-operative antibiotics, white blood cell count, and temperature at the time of conversion of intravenous (IV) to oral antibiotics were compiled. IAIs were assessed as the final outcome. RESULTS Two hundred sixty six patients underwent appendectomy-188 for simple appendicitis and 78 for complicated appendicitis. There were 18 IAIs (6.8%) overall, 10 (12.8%) after complicated appendicitis and eight (4.2%) after simple appendicitis. Prolonging antibiotics beyond the operation in the simple appendicitis group did not alter the incidence of IAI. Similarly, in the complicated appendicitis group, prolonging antibiotics beyond five days did not alter the incidence of IAI. Furthermore, in patients with complicated appendicitis, the presence of leukocytosis, fever, or both when IV antibiotics were converted to oral drugs was associated with the development of IAI (p=0.013). CONCLUSION In simple appendicitis, post-operative antibiotics may not be beneficial at all. In complicated appendicitis, prolonging the course of antibiotics was not associated with a reduced IAI rate. However, cessation of IV antibiotics when fever or leukocytosis was present was associated with IAI development.

Energy Expenditure After Liver Resection Validation of a Mobile Device for Estimating Resting Energy Expenditure and an Investigation of Energy Expenditure Change After Liver Resection

Background: Resting energy expenditure (REE) is the major component of total energy expenditure. REE is traditionally performed by indirect calorimetry (IC) and is not well investigated after liver surgery. A mobile device (SenseWear Armband [SWA]) has been validated when estimating REE in other clinical settings but not liver resection. The aims of this study are to validate SWA vs IC, quantify REE change following liver resection, and determine factors associated with REE change. Materials and Methods: Patients listed for open liver resection prospectively underwent IC and SWA REE recordings pre- and postoperatively. In addition, the SWA was worn continuously postoperatively to estimate daily REE for the first 5 postoperative days. To determine acceptability of the SWA, validation analysis was performed. To assess REE change, peak postoperative REE was compared with preoperative levels. Factors associated with REE change were also analyzed. Results: SWA showed satisfactory validity compared with IC when estimating REE, although postoperatively, the 95% levels of agreement (–5.56 to 3.18 kcal/kg/d) may introduce error. Postoperative REE (median, 23.5 kcal/kg/d; interquartile range [IQR], 22.6–25.7 kcal/kg/d) was significantly higher than predicted REE (median, 19.7 kcal/kg/d; IQR, 19.1–21.0 kcal/kg/d; P < .0001). Median REE rise was 11% (IQR, –1% to 25%). Factors associated with REE rise of >11% were age (P = .017) and length of operation (P = .03). Conclusions: SWA offers a suitable alternative to IC when estimating postoperative REE, but the magnitude of the error (8.74 kcal/kg/d) could hinder its accuracy. REE quantification after liver resection is important to identify patients who could be prone to energy imbalance and therefore malnutrition.

Short-term outcomes after liver resection for malignant and benign disease in the age of ERAS

INTRODUCTION Enhanced Recovery After Surgery protocols have been implemented effectively after liver resection and provide benefits in terms of general morbidity rates. In order to optimise peri-operative care protocols and minimise morbidity, further investigation is required to identify factors associated with poor outcome after liver resection. METHODS A retrospective analysis of patients undergoing liver resection and enhanced recovery care between January 2006 and September 2012 was conducted. Data were collected on patient outcome and demographics, operative and pathological details. Univariate and multivariate analyses were performed to determine independent predictors of adverse outcome. RESULTS 603 patients underwent liver resection during the study period. Morbidity and mortality rates were 34.3% and 1.5% respectively. The only predictor of major morbidity was extended resection (OR 4.079; 95% CI 2.177-7.642). CONCLUSIONS Extended resection is associated with major morbidity. When determining optimum peri-operative care, ERAS protocols must incorporate care components that can mitigate against morbidity associated with extended resection.

Acetaminophen metabolism after liver resection: A prospective case–control study

BACKGROUND The effect of liver resection on acetaminophen metabolism and whether it is affected by residual liver volume is poorly understood. METHODS We investigated the effects of liver resection on acetaminophen metabolism in a single centre, prospective observational, case-control study of inpatients. Patients undergoing liver resection were administered therapeutic post-operative acetaminophen. Glutathione and urinary acetaminophen metabolites were measured over the first three post-operative days and compared between patients with low (Group A) and high (Group B) residual liver volume. RESULTS 41 patients (41% female, median age 62 [IQR 53-72] years) were included. Mean urinary cysteine levels increased significantly from post-operative day 1 to 2 (578.0 mg/day 95% CI 478.9-677.1 vs. 775.4 mg/day, 95% CI 625.7-925.1; p=0.03). Group A (n=11) had significantly higher median levels of cysteine (day 1, 464.3 mg/day [IQR 355.6-582.0]; day 3, 717.6 mg/day [IQR 423.5-1104.0]) compared to Group B (n=11): day 1, 545.4 mg/day (IQR 346.9-843.5); day 3, 508.1mg/day (IQR 390.8-788.4; p=0.048). No significant difference was observed in glutathione or 5-oxoproline levels between the groups. CONCLUSION Low residual liver volume results in altered acetaminophen metabolism, however, no evidence of glutathione deficiency was observed. Therapeutic acetaminophen is safe after major liver resection provided liver function is adequate.