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NSAID administration post colorectal surgery increases anastomotic leak rate: systematic review/meta-analysis.
Modasi, A, Pace, D, Godwin, M, Smith, C, Curtis, B
Surgical endoscopy. 2019;(3):879-885
Abstract
BACKGROUND Current enhanced recovery guidelines suggest that opioid sparing medications should be used for analgesia whenever possible following colorectal surgery. The present study aims to assess whether post-operative NSAID use is associated with an increased anastomotic leak rate after a colonic or rectal anastomosis. METHODS A systematic review was performed for studies investigating anastomotic leak rate following NSAID use vs control after colonic or rectal anastomosis. Meta-analysis was performed to assess for overall risk of anastomotic leak with NSAID use, as well as sub-group analysis to compare selective vs non-selective NSAIDs and drug-specific NSAID safety profiles. RESULTS Seven studies were included in the final review. Use of an NSAID post-operatively was associated with an overall increased risk of anastomotic leakage [OR 1.58 (1.23, 2.03), P = 0.0003]. Non-selective NSAIDs were associated with an increased risk [OR 1.79 (1.47, 2.18), P < 0.00001], but selective NSAIDs were not. The non-selective NSAID diclofenac was associated with an increased leak rate [OR 2.79 (1.96, 3.96), P < 0.00001], but ketorolac was not [OR 1.36 (0.89, 2.06), P = 0.16]. CONCLUSIONS Great caution must be taken when prescribing NSAIDs following colonic or rectal anastomotic creation. The safety profile varies within the NSAID class and further research is needed to clarify which NSAIDs are safe for use and which are not.
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Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.
Bashashati, M, Moossavi, S, Cremon, C, Barbaro, MR, Moraveji, S, Talmon, G, Rezaei, N, Hughes, PA, Bian, ZX, Choi, CH, et al
Neurogastroenterology and motility. 2018;(1)
Abstract
BACKGROUND & AIMS Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. METHODS PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I2 statistics where I2 ≤ 50% and I2 > 50% indicated fixed and random effect models, respectively. KEY RESULTS Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3+ T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P = .001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P = .002). This was possibly in relation to higher CD4+ T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P = .04) as there were no differences in CD8+ T cells. CONCLUSIONS & INFERENCES Mast cells and CD3+ T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation.
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Goal-directed fluid therapy versus conventional fluid therapy in colorectal surgery: A meta analysis of randomized controlled trials.
Xu, C, Peng, J, Liu, S, Huang, Y, Guo, X, Xiao, H, Qi, D
International journal of surgery (London, England). 2018;:264-273
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Abstract
OBJECTIVES This meta-analysis was conducted to compare the effects of goal-directed fluid therapy (GDFT) versus conventional fluid therapy (CFT) in colorectal surgery on patients' postoperative outcome and to detect whether the results differ between studies with the Enhanced Recovery After Surgery (ERAS) protocol and those without, between studies using different devices for GDFT, or between different surgical approaches (laparoscopy or laparotomy). METHODS The Cochrane Library, PubMed, Embase, Wanfang Data and ClinicalTrials.com were searched for studies from January,1990 to February, 2018. Randomized controlled trials (RCTs) comparing both two abovementioned fluid therapy protocols in colorectal surgery were included. The primary outcome was 30-day mortality after surgery. Secondary outcomes were length of hospital stay (LOS), complication rate, ICU admission and gastrointestinal indicators. RESULTS Eleven studies were included, including a total of 1281 patients: the GDFT group included 624 patients and the control group included 657 patients. No significant differences were found between groups in 30-day mortality (relative risk, RR 0.86,0.28 to 2.63, P = 0.79), LOS (weighted mean difference, WMD 0.22,-0.1 to 0.55, P = 0.18), and ICU admission (RR 0.42, 0.17 to 1.04, P = 0.06). However, the GDFT group had a lower complication rate (RR 0.84,0.71 to 0.99, P = 0.04). In subgroup analyses, time to first flatus and time to tolerate an oral diet were shorter in GDFT group than the control group in studies who did not use the ERAS protocol. No publication bias was identified according to Begg's test. CONCLUSION Compared with conventional fluid therapy, GDFT may not improve patients' postoperative outcome in colorectal surgery. However, the improvement of gastrointestinal function associated with GDFT over conventional fluid therapy was significant in the surgeries that did not use the ERAS protocol.
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Nonsteroidal anti-inflammatory drugs reduce the time to recovery of gut function after elective colorectal surgery: a systematic review and meta-analysis.
Milne, TGE, Jaung, R, O'Grady, G, Bissett, IP
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2018;(8):O190-O198
Abstract
AIM: Postoperative ileus causes significant patient morbidity after abdominal surgery. Some evidence suggests nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce time to gut recovery, but there has not been a meta-analysis to assess their efficacy. This systematic review and meta-analysis aimed to determine the benefit of NSAIDs for recovery of postoperative gut function in patients undergoing elective colorectal surgery. METHOD MEDLINE, EMBASE, CENTRAL and reference lists were searched with no date or language restrictions. Randomized controlled trials comparing the use of NSAIDs with placebo in the perioperative or postoperative period were identified. Included studies reported outcomes relevant to gut function: time to pass flatus or stool and time to tolerate an oral diet. The mean difference in time from surgery until passage of flatus, stool and tolerance of diet were meta-analysed using a random-effects model in RevMan 5.3. RESULTS This study identified 992 relevant articles. Five randomized controlled trials on patients undergoing elective colorectal surgery met our inclusion criteria and were meta-analysed. Compared with placebo, NSAIDs significantly improved the time to pass flatus (mean difference -9.44 h, 95% CI: -17.22, -1.65, I2 = 70%, P = 0.02), time to pass stool (mean difference -12.09 h, 95% CI: -17.16, -7.02, I2 = 0%, P < 0.001) and time to tolerate a diet (mean difference -11.95 h, 95% CI: -18.66, -5.24, I2 = 0%, P < 0.001). CONCLUSION NSAIDs significantly improve time to gut recovery after elective colorectal surgery. Current evidence is not adequate to identify whether selective or nonselective drugs should be recommended. Further high-power studies using selective drugs are required.
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Early enteral nutrition within 24 hours of lower gastrointestinal surgery versus later commencement for length of hospital stay and postoperative complications.
Herbert, G, Perry, R, Andersen, HK, Atkinson, C, Penfold, C, Lewis, SJ, Ness, AR, Thomas, S
The Cochrane database of systematic reviews. 2018;(10):CD004080
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Abstract
BACKGROUND This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation. OBJECTIVES To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews. SELECTION CRITERIA We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA). MAIN RESULTS We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I2 = 81, %, Chi2 = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I2 = 0%, Chi2 = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I2 = 0%, Chi2 = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence). AUTHORS' CONCLUSIONS This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.