Perioperative Probiotics or Synbiotics in Adults Undergoing Elective Abdominal Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To define the impact of perioperative treatment with probiotics or synbiotics on postoperative outcome in patients undergoing abdominal surgery. BACKGROUND: Postoperative surgical infection accounts for a third of all cases of sepsis, and is a leading cause of morbidity and mortality. Probiotics, prebiotics, and synbiotics (preparations that combine probiotics and prebiotics) are nutritional adjuncts that are emerging as novel therapeutic modalities for preventing surgical infections. However, current evidence on their effects is conflicting. METHODS: A comprehensive search of the PubMed, Embase, and WHO Global Index Medicus electronic databases was performed to identify randomized controlled trials evaluating probiotics or synbiotics in adult patients undergoing elective colorectal, upper gastrointestinal, transplant, or hepatopancreaticobiliary surgery. Bibliographies of studies were also searched. The primary outcome measure was incidence of postoperative infectious complications. Secondary outcomes included incidence of noninfectious complications, mortality, length of hospital stay, and any treatment-related adverse events. Quantitative pooling of the data was undertaken using a random effects model. RESULTS: A total of 34 randomized controlled trials reporting on 2723 participants were included. In the intervention arm, 1354 patients received prebiotic or symbiotic preparations, whereas 1369 patients in the control arm received placebo or standard care. Perioperative administration of either probiotics or synbiotics significantly reduced the risk of infectious complications following abdominal surgery [relative risk (RR) 0.56; 95% confidence interval (CI) 0.46-0.69; P < 0.00001, n = 2723, I = 42%]. Synbiotics showed greater effect on postoperative infections compared with probiotics alone (synbiotics RR: 0.46; 95% CI: 0.33-0.66; P < 0.0001, n = 1399, I = 53% probiotics RR: 0.65; 95% CI: 0.53-0.80; P < 0.0001, n = 1324, I = 18%). Synbiotics but not probiotics also led to a reduction in total length of stay (synbiotics weighted mean difference: -3.89; 95% CI: -6.60 to -1.18 days; P = 0.005, n = 535, I = 91% probiotics RR: -0.65; 95% CI: -2.03-0.72; P = 0.35, n = 294, I = 65%). There were no significant differences in mortality (RR: 0.98; 95% CI: 0.54-1.80; P = 0.96, n = 1729, I = 0%) or noninfectious complications between the intervention and control groups. The preparations were well tolerated with no significant adverse events reported. CONCLUSIONS: Probiotics and synbiotics are safe and effective nutritional adjuncts in reducing postoperative infective complications in elective abdominal surgery. The treatment effects are greatest with synbiotics.

Antibiotics Versus Appendicectomy for the Treatment of Uncomplicated Acute Appendicitis: An Updated Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Uncomplicated acute appendicitis has been managed traditionally by early appendicectomy. However, recently, there has been increasing interest in the potential for primary treatment with antibiotics, with studies finding this to be associated with fewer complications than appendicectomy. The aim of this study was to compare outcomes of antibiotic therapy with appendicectomy for uncomplicated acute appendicitis. METHOD: This meta-analysis of randomised controlled trials included adult patients presenting with uncomplicated acute appendicitis treated with antibiotics or appendicectomy. The primary outcome measure was complications. Secondary outcomes included treatment efficacy, hospital length of stay (LOS), readmission rate and incidence of complicated appendicitis. RESULTS: Five randomised controlled trials with a total of 1430 participants (727 undergoing antibiotic therapy and 703 undergoing appendicectomy) were included. There was a 39 % risk reduction in overall complication rates in those treated with antibiotics compared with those undergoing appendicectomy (RR 0.61, 95 % CI 0.44-0.83, p = 0.002). There was no significant difference in hospital LOS (mean difference 0.25 days, 95 % CI -0.05 to 0.56, p = 0.10). In the antibiotic cohort, 123 of 587 patients initially treated successfully with antibiotics were readmitted with symptoms suspicious of recurrent appendicitis. The incidence of complicated appendicitis was not increased in patients who underwent appendicectomy after "failed" antibiotic treatment (10.8 %) versus those who underwent primary appendicectomy (17.9 %). CONCLUSION: Increasing evidence supports the primary treatment of acute uncomplicated appendicitis with antibiotics, in terms of complications, hospital LOS and risk of complicated appendicitis. Antibiotics should be prescribed once a diagnosis of acute appendicitis is made or considered.

A meta-analysis of the effect of combinations of immune modulating nutrients on outcome in patients undergoing major open gastrointestinal surgery.

BACKGROUND: Immune modulating nutrition (IMN) has been shown to reduce complications after major surgery, but strong evidence to recommend its routine use is still lacking. OBJECTIVE: The aim of this meta-analysis was to evaluate the impact of IMN combinations on postoperative infectious and noninfectious complications, length of hospital stay, and mortality in patients undergoing major open gastrointestinal surgery. METHODS: Randomized controlled trials published between January 1980 and February 2011 comparing isocaloric and isonitrogenous enteral IMN combinations with standard diet in patients undergoing major open gastrointestinal surgery were included. The quality of evidence and strength of recommendation for each postoperative outcome were assessed using the GRADE approach and the outcome measures were analyzed with RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Twenty-six randomized controlled trials enrolling 2496 patients (1252 IMN and 1244 control) were included. The meta-analysis suggests strong evidence in support of decrease in the incidence of postoperative infectious [risk ratio (RR) (95% confidence interval [CI]): 0.64 (0.55, 0.74)] and length of hospital stay [mean difference (95% CI): -1.88 (-2.91, -0.84 days)] in those receiving IMN. Even though significant benefit was observed for noninfectious complications [RR (95% CI): 0.82 (0.71, 0.95)], the quality of evidence was low. There was no statistically significant benefit on mortality [RR (95% CI): 0.83 (0.49, 1.41)]. CONCLUSIONS: IMN is beneficial in reducing postoperative infectious and noninfectious complications and shortening hospital stay in patients undergoing major open gastrointestinal surgery.

Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function.

BACKGROUND & AIMS: This post hoc study aimed to determine whether major elective abdominal surgery had any acute impact on mitochondrial pyruvate dehydrogenase complex (PDC) activity and maximal mitochondrial ATP production rates (MAPR) in a large muscle group (vastus lateralis -VL) distant to the site of surgical trauma. METHODS: Fifteen patients undergoing major elective open abdominal surgery were studied. Muscle biopsies were obtained after the induction of anesthesia from the VL immediately before and after surgery for the determination of PDC and maximal MAPR (utilizing a variety of energy substrates). RESULTS: Muscle PDC activity was reduced by >50% at the end of surgery compared with pre-surgery (p < 0.05). Muscle MAPR were comprehensively suppressed by surgery for the substrate combinations: glutamate + succinate; glutamate + malate; palmitoylcarnitine + malate; and pyruvate + malate (all p < 0.05), and could not be explained by a lower mitochondrial yield. CONCLUSIONS: PDC activity and mitochondrial ATP production capacity were acutely impaired in muscle distant to the site of surgical trauma. In keeping with the limited data available, we surmise these events resulted from the general anesthesia procedures employed and the surgery related trauma. These findings further the understanding of the acute dysregulation of mitochondrial function in muscle distant to the site of major surgical trauma in patients, and point to the combination of general anesthesia and trauma related inflammation as being drivers of muscle metabolic insult that warrants further investigation. CLINICAL TRIAL REGISTRATION: Registered at (NCT01134809).

Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis.

BACKGROUND: Antibiotic treatment has been shown to be effective in treating selected patients with acute appendicitis, and three randomized controlled trials (RCTs) have compared the efficacy of antibiotic therapy alone with that of surgery for acute appendicitis. The purpose of this meta-analysis of RCTs was to assess the outcomes with these two therapeutic modalities. METHODS: All RCTs comparing antibiotic therapy alone with surgery in patients over 18 years of age with suspected acute appendicitis were included. Patients with suspected perforated appendix or peritonitis, and those with an allergy to antibiotics had been excluded in the RCTs. The outcome measures studied were complications, length of hospital stay, and readmissions. RESULTS: Meta-analysis of RCTs of antibiotic therapy versus surgery showed a trend toward a reduced risk of complications in the antibiotic-treated group [RR (95%CI): 0.43 (0.16, 1.18) p = 0.10], without prolonging the length of hospital stay [mean difference (inverse variance, random, 95% CI): 0.11 (-0.22, 0.43) p = 0.53]. Of the 350 patients randomized to the antibiotic group, 238 (68%) were treated successfully with antibiotics alone and 38 (15%) were readmitted. The remaining 112 (32%) patients randomized to antibiotic therapy crossed over to surgery for a variety of reasons. At 1 year, 200 patients in the antibiotic group remained asymptomatic. CONCLUSIONS: This meta-analysis suggests that although antibiotics may be used as primary treatment for selected patients with suspected uncomplicated appendicitis, this is unlikely to supersede appendectomy at present. Selection bias and crossover to surgery in the RCTs suggest that appendectomy is still the gold standard therapy for acute appendicitis.

Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery.

BACKGROUND & AIMS: Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation. METHODS: Fifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis - RA) and remote to the site of surgery (vastus lateralis - VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation. RESULTS: Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4 (7.8-fold, P < 0.05), TNF-α (16.5-fold, P < 0.05) and IL-6 (1058-fold, P < 0.001). A similar, albeit blunted, response was observed in VL. Surgery also increased expression of proteins linked to inflammation (IL-6; 6-fold, P < 0.01), protein degradation (MAFbx; 4.5-fold, P < 0.5), and blunted carbohydrate oxidation (PDK4; 4-fold, P < 0.05) in RA but not VL. Increased systemic inflammation (TNF-α, P < 0.05; IL-6, P < 0.001), and impaired postoperative glucose tolerance (P < 0.001), but not bacteraemia (although gut permeability was increased significantly, P < 0.05) or increased plasma cortisol, were noted 48 h postoperatively. CONCLUSIONS: A systemic postoperative proinflammatory response was accompanied by muscle inflammation and metabolic dysregulation both local and remote to the site of surgery, and was not accompanied by bacteraemia. CLINICAL TRIAL REGISTRATION: Registered at http://clinicaltrials.gov (NCT01134809).

Systematic review of the impact of HbA1c on outcomes following surgery in patients with diabetes mellitus.

BACKGROUND & AIMS: Diabetes is a significant risk factor for surgical complications and also increases the prevalence of comorbidities, thereby increasing surgical risk. The aim of this systematic review was to establish the relationship between long-term preoperative glycemic control as measured by HbA1c and postoperative complications. METHODS: A systematic search was conducted to source articles published between 1980 and 2014 pertinent to the review. Full-text articles were included if they met the pre-determined criteria as determined by two reviewers. Studies reporting the impact of preoperative HbA1c levels on postoperative outcomes in all disciplines of surgery were included. RESULTS: Twenty studies, including a total of 19,514 patients with diabetes mellitus from a range of surgical specialties, were suitable for inclusion. Preoperative glycemic control did not have a bearing on 30-day mortality. There were no significant differences in the incidence of stroke, venous thromboembolic disease, hospital readmission and ITU length of stay based on glycemic control. The majority of studies suggested no link between preoperative HbA1c levels and acute kidney injury or need for postoperative dialysis, dysrhythmia, infection not related to the surgical site and total hospital length of stay. The literature was highly variable with regards to myocardial events, surgical site infection and reoperation rates. CONCLUSIONS: Elevated preoperative HbA1c was not definitively associated with increased postoperative morbidity or mortality in patients with diabetes mellitus. The studies included in this review were relatively heterogeneous, predominantly retrospective, and often contained small patient numbers, suggesting that good quality evidence is necessary.

A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery.

BACKGROUND & AIMS: Whilst preoperative carbohydrate treatment (PCT) results in beneficial physiological effects, the effects on postoperative clinical outcomes remain unclear and were studied in this meta-analysis. METHODS: Prospective studies that randomised adult non-diabetic patients to either PCT (≥50 g oral carbohydrates 2-4 h pre-anaesthesia) or control (fasted/placebo) were included. The primary outcome was length of hospital stay. Secondary outcomes included development of postoperative insulin resistance, complications, nausea and vomiting. Methodological quality was assessed using GRADEpro® software. RESULTS: Twenty-one randomised studies of 1685 patients (733 PCT: 952 control) were included. No overall difference in length of stay was noted for analysis of all studies or subgroups of patients undergoing surgery with an expected hospital stay ≤2 days or orthopaedic procedures. However, patients undergoing major abdominal surgery following PCT had reduced length of stay [mean difference, 95% confidence interval: -1.08 (-1.87 to -0.29); I² = 60%, p = 0.007]. PCT reduced postoperative insulin resistance with no effects on in-hospital complications over control (risk ratio, 95% confidence interval, 0.88 (0.50-1.53), I² = 41%; p = 0.640). There was significant heterogeneity amongst studies and, therefore, quality of evidence was low to moderate. CONCLUSIONS: PCT may be associated with reduced length of stay in patients undergoing major abdominal surgery, however, the included studies were of low to moderate quality.

Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials.

OBJECTIVE: To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. DESIGN: Meta-analysis of randomised controlled trials. POPULATION: Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. INTERVENTIONS: Antibiotic treatment versus appendicectomy. OUTCOME MEASURES: The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. RESULTS: Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I(2)=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I(2)=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. CONCLUSION: Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis.

A meta-analysis of randomised controlled trials of intravenous fluid therapy in major elective open abdominal surgery: getting the balance right.

The terminology used for describing intervention groups in randomised controlled trials (RCT) on the effect of intravenous fluid on outcome in abdominal surgery has been imprecise, and the lack of standardised definitions of the terms 'standard', 'restricted' and 'liberal' has led to some confusion and difficulty in interpreting the literature. The aims of this paper were to clarify these definitions and to use them to perform a meta-analysis of nine RCT on primarily crystalloid-based peri-operative intravenous fluid therapy in 801 patients undergoing elective open abdominal surgery. Patients who received more or less fluids than those who received a 'balanced' amount were considered to be in a state of 'fluid imbalance'. When 'restricted' fluid regimens were compared with 'standard or liberal' fluid regimens, there was no difference in post-operative complication rates (risk ratio 0.83 (95% CI 0.49, 1.39, P = 0.47) [corrected] or length of hospital stay (weighted mean difference (WMD) - 1.77 (95% CI - 4.36, 0.81) d, P = 0.18). However, when the fluid regimens were reclassified and patients were grouped into those who were managed in a state of fluid 'balance' or 'imbalance', the former group had significantly fewer complications (risk ratio 0·59 (95% CI 0·44, 0·81), P=0·0008) and a shorter length of stay (WMD -3·44 (95% CI -6·33, -0·54) d, P=0·02) than the latter. Using imprecise terminology, there was no apparent difference between the effects of fluid-restricted and standard or liberal fluid regimens on outcome in patients undergoing elective open abdominal surgery. However, patients managed in a state of fluid balance fared better than those managed in a state of fluid imbalance.

Enhanced recovery after surgery: the future of improving surgical care.

Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway designed to attenuate the stress response during the patients' journey through a surgical procedure to facilitate the maintenance of preoperative bodily compositions and organ function and in doing so achieve early recovery. The key factors that keep patients in hospital after uncomplicated major abdominal surgery include the need for parenteral analgesia, intravenous fluids secondary to persistent gut dysfunction, and bed rest caused by lack of mobility. The elements of the ERAS pathways are aimed to address these issues and the interventions that facilitate early recovery cover all three phases of the perioperative period during the patients' journey. They also provide clear guidance to all members of the clinical team.

The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: The aim of the Enhanced Recovery After Surgery (ERAS) pathway is to attenuate the stress response to surgery and enable rapid recovery. The objective of this meta-analysis was to study the differences in outcomes in patients undergoing major elective open colorectal surgery within an ERAS pathway and those treated with conventional perioperative care. METHODS: Medline, Embase and Cochrane database searches were performed for relevant studies published between January 1966 and November 2009. All randomized controlled trials comparing ERAS with conventional perioperative care were selected. The outcome measures studied were length of hospital stay, complication rates, readmission rates and mortality. RESULTS: Six randomized controlled trials with 452 patients were included. The number of individual ERAS elements used ranged from 4 to 12, with a mean of 9. The length of hospital stay [weighted mean difference (95% confidence interval): -2.55 (-3.24, -1.85)] and complication rates [relative risk (95% confidence interval): 0.53 (0.44, 0.64)] were significantly reduced in the enhanced recovery group. There was no statistically significant difference in readmission and mortality rates. CONCLUSION: ERAS pathways appear to reduce the length of stay and complication rates after major elective open colorectal surgery without compromising patient safety.