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Perioperative Probiotics or Synbiotics in Adults Undergoing Elective Abdominal Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Chowdhury, AH, Adiamah, A, Kushairi, A, Varadhan, KK, Krznaric, Z, Kulkarni, AD, Neal, KR, Lobo, DN
Annals of surgery. 2020;(6):1036-1047
Abstract
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.
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Perioperative nonhormonal pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy: a systematic review and network meta-analysis.
Samy, A, Raslan, AN, Talaat, B, El Lithy, A, El Sharkawy, M, Sharaf, MF, Hussein, AH, Amin, AH, Ibrahim, AM, Elsherbiny, WS, et al
Fertility and sterility. 2020;(1):224-233.e6
Abstract
OBJECTIVE To synthesize evidence on the most effective pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy. DESIGN Systematic review and network meta-analysis of randomized controlled trials (RCTs). SETTING Not applicable. PATIENTS Trials assessing efficacy of pharmacological interventions during different types of myomectomy. INTERVENTIONS Misoprostol, oxytocin, vasopressin, tranexamic acid (TXA), epinephrine, or ascorbic acid. MAIN OUTCOME MEASURES Intraoperative blood loss and need for blood transfusion. RESULTS The present review included 26 randomized control trials (RCTs) (N = 1627). For minimally invasive procedures (9 RCTs; 474 patients), network meta-analysis showed that oxytocin (mean difference [MD] -175.5 mL, 95% confidence interval [CI] -30.1.07, -49.93), ornipressin (MD -149.6 mL, 95% CI - 178.22, -120.98), misoprostol, bupivacaine plus epinephrine, and vasopressin were effective in reducing myomectomy blood loss, but the evidence is of low quality. Ranking score of treatments included in subgroup analysis of minimally invasive myomectomy showed that oxytocin ranked first in reducing blood loss, followed by ornipressin. For open myomectomy (17 RCTs; 1,153 patients), network meta-analysis showed that vasopressin plus misoprostol (MD -652.97 mL, 95% CI - 1113.69, -174.26), oxytocin, TXA, and misoprostol were effective; however, the evidence is of low quality. Vasopressin plus misoprostol ranked first in reducing blood loss during open myomectomy (P = .97). CONCLUSION There is low-quality evidence to support uterotonics, especially oxytocin, and peripheral vasoconstrictors as effective options in reducing blood loss and need for blood transfusion during minimally invasive myomectomy. Oxytocin is the most effective intervention in minimally invasive myomectomy. For open myomectomy, a combination of uterotonics and peripheral vasoconstrictors is needed to effectively reduce blood loss.
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Effect of Perioperative Glucose-Insulin-Potassium Therapy in Patients Undergoing On-Pump Cardiac Surgery: A Meta-Analysis.
Li, Q, Yang, J, Zhang, J, Yang, C, Fan, Z, Yang, Y, Zheng, T, Yang, J
The heart surgery forum. 2020;(1):E063-E069
Abstract
OBJECTIVE The role of glucose-insulin-potassium (GIK) infusion during cardiac surgery has held interest for so many years without a clear answer. The aim of this meta-analysis was to evaluate the effect of GIK therapy on outcomes in patients undergoing on-pump cardiac surgery. METHODS A comprehensive online review was performed in The Web of Science, Embase, Medline, PubMed, and The Cochrane Library databases from 2000 to 2019. Eligible studies included randomized controlled trials (RCTs) that compared GIK treatment with placebo or standard care during on-pump cardiac surgery. Risk ratios (RR) were used for binary outcomes and mean difference (MD) was used for continuous variables; both with their 95% confidence intervals (CI). RESULTS A total of 18 RCTs involving 2,131 patients met the inclusion criteria. Compared with the control group, the GIK treatment significantly reduced in-hospital mortality (RR = 0.56, 95% CI: 0.32-0.97; P = .04), postoperative myocardial infarctions (MI) (RR = 0.71, 95% CI: 0.56-0.91; P = .006), the use of inotropic support (RR = 0.53, 95% CI: 0.45-0.63; P < .00001), and length of stay in the intensive care unit (ICU) (MD = -0.33, 95% CI: -0.52--0.14; P = .0007). Moreover, GIK treatment seemed to be associated with fewer postoperative atrial fibrillation (AF) (RR = 0.81, 95% CI: 0.64-1.03; P = .09). CONCLUSIONS In patients undergoing on-pump cardiac surgery, GIK infusion has a beneficial role in mortality during hospital stay and demonstrates superior efficacy versus standard care for reduction in postoperative MI, AF, ICU length of stay as well as inotropic agent requirements.
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Clinical Efficacy of Perioperative Immunonutrition Containing Omega-3-Fatty Acids in Patients Undergoing Hepatectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Gao, B, Luo, J, Liu, Y, Zhong, F, Yang, X, Gan, Y, Su, S, Li, B
Annals of nutrition & metabolism. 2020;(6):375-386
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Abstract
BACKGROUND The effect of immunonutrition in patients undergoing hepatectomy remains unclear. This meta-analysis aimed to assess the impact of immunonutrition on postoperative clinical outcomes in patients undergoing hepatectomy. METHODS A literature search of PubMed, Cochrane Library, Web of Science, and Embase databases was performed to identify all randomized controlled trials (RCTs) exploring the effect of perioperative immunonutrition in patients undergoing hepatectomy until the end of March 10, 2020. Quality assessment and data extraction of RCTs were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. RESULTS Nine RCTs involving a total of 966 patients were finally included. This meta-analysis showed that immunonutrition significantly reduced the incidences of overall postoperative complications (OR = 0.57, 95% CI: 0.34-0.95; p = 0.03), overall postoperative infectious complications (OR = 0.53, 95% CI: 0.37-0.75; p = 0.0003), and incision infection (OR = 0.50, 95% CI: 0.28-0.89; p = 0.02), and it shortened the length of hospital stay (MD = -3.80, 95% CI: -6.59 to -1.02; p = 0.007). There were no significant differences in the incidences of pulmonary infection (OR = 0.60, 95% CI: 0.32-1.12; p = 0.11), urinary tract infection (OR = 1.30, 95% CI: 0.55-3.08; p = 0.55), liver failure (OR = 0.54, 95% CI: 0.23-1.24; p = 0.15), and postoperative mortality (OR = 0.69, 95% CI: 0.26-1.83; p = 0.46). CONCLUSION Given its positive impact on postoperative complications and the tendency to shorten the length of hospital stay, perioperative immunonutrition should be encouraged in patients undergoing hepatectomy.
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Perioperative immunonutrition in esophageal cancer patients undergoing esophagectomy: the first meta-analysis of randomized clinical trials.
Mingliang, W, Zhangyan, K, Fangfang, F, Huizhen, W, Yongxiang, L
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2020;(4)
Abstract
Although several randomized controlled trials have been published in recent years, the effect of perioperative immunonutrition in esophageal cancer (EC) patients remains unclear. This initial meta-analysis was conducted to assess whether perioperative enteral immunonutrition reduces postoperative complications in patients undergoing esophagectomy for EC. Relevant randomized controlled trials published before 1st September 2019 were retrieved from the Cochrane Library, PubMed, and EMBASE databases. After the literature was screened, two researchers extracted the information and data from eligible studies according to predefined selection criteria. Obtained data were pooled and analyzed by RevMan 5.3 software. The results were presented as risk ratios (RRs) with 95% confidence intervals (CIs). The heterogeneity among studies was tested by I2 test. Seven high-quality randomized controlled trials were included, with a total of 606 patients, 311 of whom received immunonutrition before and after surgery, while 295 received perioperative standard nutrition. No significant difference was observed between the two groups in the incidence of postoperative infection complications, including total infection complications (RR = 0.97, CI: 0.78-1.20, P = 0.76), pneumonia (RR = 0.97, CI: 0.71-1.33, P = 0.84), wound infection (RR = 0.80, CI: 0.46-1.40, P = 0.44), sepsis (RR = 1.35, CI: 0.67-2.71, P = 0.40), and urinary tract infection (RR = 0.87, CI: 0.54-1.40, P = 0.56). The prevalence of anastomotic leakage in the two groups was 9.4 and 5.4%, but the difference was not statistically significant (RR = 0.59, CI: 0.33-1.04, P = 0.07). Perioperative enteral immunonutrition provided no benefit in terms of the incidence of infection complications and anastomotic leakage in EC patients undergoing esophagectomy. Further large-scale randomized controlled trials are needed to confirm this conclusion.
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Effect of Perioperative Nutritional Supplementation on Postoperative Complications-Systematic Review and Meta-Analysis.
Zhang, B, Najarali, Z, Ruo, L, Alhusaini, A, Solis, N, Valencia, M, Sanchez, MIP, Serrano, PE
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2019;(8):1682-1693
Abstract
BACKGROUND Perioperative carbohydrate loading, increased protein intake, and immunonutrition may decrease postoperative complications. Studies on the topic have led to controversial results. METHODS We searched Medline, EMBASE, and CENTRAL up to August 2018 for randomized trials comparing the effect of perioperative nutritional supplements (intervention) versus control on postoperative complications in patients undergoing gastrointestinal cancer surgery. Secondary outcomes included infectious complications and length of hospital stay (LOS). Random effects model was used to estimate the pooled risk ratio (RR) of treatment effects. Pooled mean difference (MD) was used to compare LOS. Heterogeneity was assessed using I2. Sources of heterogeneity were explored through subgroup analysis by nutritional supplementation protocol, type of surgery, and type of nutritional supplement. Risk of bias and quality of the evidence were assessed. RESULTS Of 3951 articles, we identified 56 trials (n = 6370). Perioperative nutrition was associated with a lower risk of postoperative complications (RR 0.74, 95% confidence interval (CI) 0.69-0.80); postoperative infections (RR 0.71, 95% CI 0.64-0.79, n = 4582); and postoperative non-infectious complications (RR 0.79, 95% CI 0.71-0.87, n = 4883). There were no significant heterogeneity outcomes analyzed (I2 = 14%, 1%, and 7%, respectively). LOS was shorter for the intervention group, MD - 1.58 days; 95% CI - 1.83 to - 1.32; I2 = 89%). Subgroup analysis did not identify sources of heterogeneity. The quality of evidence for postoperative complications was high and for LOS was moderate. CONCLUSION Perioperative nutritional optimization decreases the risk of postoperative infectious and non-infectious complications. It also decreases LOS in patients undergoing gastrointestinal cancer surgery, but these findings should be taken with caution given the high heterogeneity.
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Impact of enhanced recovery after surgery protocols versus standard of care on perioperative outcomes of radical cystectomy: a systematic review and meta-analysis of comparative studies.
Giannarini, G, Crestani, A, Inferrera, A, Rossanese, M, Subba, E, Novara, G, Ficarra, V
Minerva urologica e nefrologica = The Italian journal of urology and nephrology. 2019;(4):309-323
Abstract
INTRODUCTION Among the measures taken in the recent years to reduce the morbidity and improve functional recovery after radical cystectomy (RC), the optimization of perioperative care pathways is gaining a prominent role. The aim of this systematic review of the literature with meta-analysis is to assess the impact of enhanced recovery after surgery (ERAS) protocols vs. standard of care on perioperative outcomes of patients undergoing RC. EVIDENCE ACQUISITION A systematic review with meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. MEDLINE, SCOPUS and Web of Science databases were searched. Only comparative studies evaluating the impact of ERAS protocols vs. standard of care on intraoperative and postoperative outcomes of patients undergoing RC were included. Cumulative analysis was conducted using Review Manager v.5.3 software. Statistical heterogeneity was tested using the χ2 Test, and a P value <0.10 was used to indicate heterogeneity. Random-effects and fixed-effects models were used as appropriate depending on heterogeneity status. EVIDENCE SYNTHESIS A total of 27 studies were included, namely 3 randomized and 24 non-randomized controlled studies, resulting in 4712 patients, 2690 (57%) participants to some ERAS protocol and 2022 (43%) controls receiving standard of care. A number of primary and secondary outcome measures were assessed in the original studies. Pooled data showed that ERAS protocols were associated with significantly faster recovery of bowel function, faster return to regular diet and shorter hospital stay with no increase in 30-day and 90-day major complication, mortality or readmission rates compared to standard of care. The magnitude of benefit of the various ERAS protocols tested had, however, a non-negligible inter-study variability. CONCLUSIONS This systematic review with meta-analysis of comparative studies showed that ERAS protocols applied to patients undergoing RC enabled a faster recovery of bowel function, a faster return to regular diet and a shorter hospital stay with no increase in major complication or readmission rate compared to standard perioperative care. RC with ERAS protocols should be considered the new standard of care.
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Perioperative restrictive versus goal-directed fluid therapy for adults undergoing major non-cardiac surgery.
Wrzosek, A, Jakowicka-Wordliczek, J, Zajaczkowska, R, Serednicki, WT, Jankowski, M, Bala, MM, Swierz, MJ, Polak, M, Wordliczek, J
The Cochrane database of systematic reviews. 2019;(12):CD012767
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Abstract
BACKGROUND Perioperative fluid management is a crucial element of perioperative care and has been studied extensively recently; however, 'the right amount' remains uncertain. One concept in perioperative fluid handling is goal-directed fluid therapy (GDFT), wherein fluid administration targets various continuously measured haemodynamic variables with the aim of optimizing oxygen delivery. Another recently raised concept is that perioperative restrictive fluid therapy (RFT) may be beneficial and at least as effective as GDFT, with lower cost and less resource utilization. OBJECTIVES To investigate whether RFT may be more beneficial than GDFT for adults undergoing major non-cardiac surgery. SEARCH METHODS We searched the following electronic databases on 11 October 2019: Cochrane Central Register of Controlled Trials, in the Cochrane Libary; MEDLINE; and Embase. Additionally, we performed a targeted search in Google Scholar and searched trial registries (World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov) for ongoing and unpublished trials. We scanned the reference lists and citations of included trials and any relevant systematic reviews identified. SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing perioperative RFT versus GDFT for adults (aged ≥ 18 years) undergoing major non-cardiac surgery. DATA COLLECTION AND ANALYSIS Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. We resolved discrepancies by discussion and consulted a third review author if necessary. When necessary, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and for continuous outcomes as mean differences (MDs) with standard deviations (SDs). We used Review Manager 5 software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model. We used Poisson regression models to compare the average number of complications per person. MAIN RESULTS From 6396 citations, we included six studies with a total of 562 participants. Five studies were performed in participants undergoing abdominal surgery (including one study in participants undergoing cytoreductive abdominal surgery with hyperthermic intraperitoneal chemotherapy (HIPEC)), and one study was performed in participants undergoing orthopaedic surgery. In all studies, surgeries were elective. In five studies, crystalloids were used for basal infusion and colloids for boluses, and in one study, colloid was used for both basal infusion and boluses. Five studies reported the ASA (American Society of Anesthesiologists) status of participants. Most participants were ASA II (60.4%), 22.7% were ASA I, and only 16.9% were ASA III. No study participants were ASA IV. For the GDFT group, oesophageal doppler monitoring was used in three studies, uncalibrated invasive arterial pressure analysis systems in two studies, and a non-invasive arterial pressure monitoring system in one study. In all studies, GDFT optimization was conducted only intraoperatively. Only one study was at low risk of bias in all domains. The other five studies were at unclear or high risk of bias in one to three domains. RFT may have no effect on the rate of major complications compared to GDFT, but the evidence is very uncertain (RR 1.61, 95% CI 0.78 to 3.34; 484 participants; 5 studies; very low-certainty evidence). RFT may increase the risk of all-cause mortality compared to GDFT, but the evidence on this is also very uncertain (RD 0.03, 95% CI 0.00 to 0.06; 544 participants; 6 studies; very low-certainty evidence). In a post-hoc analysis using a Peto odds ratio (OR) or a Poisson regression model, the odds of all-cause mortality were 4.81 times greater with the use of RFT compared to GDFT, but the evidence again is very uncertain (Peto OR 4.81, 95% CI 1.38 to 16.84; 544 participants; 6 studies; very low-certainty evidence). Nevertheless, sensitivity analysis shows that exclusion of a study in which the final volume of fluid received intraoperatively was higher in the RFT group than in the GDFT group revealed no differences in mortality. Based on analysis of secondary outcomes, such as length of hospital stay (464 participants; 5 studies; very low-certainty evidence), surgery-related complications (364 participants; 4 studies; very low-certainty evidence), non-surgery-related complications (74 participants; 1 study; very low-certainty evidence), renal failure (410 participants; 4 studies; very low-certainty evidence), and quality of surgical recovery (74 participants; 1 study; very low-certainty evidence), GDFT may have no effect on the risk of these outcomes compared to RFT, but the evidence is very uncertain. Included studies provided no data on administration of vasopressors or inotropes to correct haemodynamic instability nor on cost of treatment. AUTHORS' CONCLUSIONS Based on very low-certainty evidence, we are uncertain whether RFT is inferior to GDFT in selected populations of adults undergoing major non-cardiac surgery. The evidence is based mainly on data from studies on abdominal surgery in a low-risk population. The evidence does not address higher-risk populations or other surgery types. Larger, higher-quality RCTs including a wider spectrum of surgery types and a wider spectrum of patient groups, including high-risk populations, are needed to determine effects of the intervention.
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Impact of enhanced recovery after surgery programs on pancreatic surgery: A meta-analysis.
Ji, HB, Zhu, WT, Wei, Q, Wang, XX, Wang, HB, Chen, QP
World journal of gastroenterology. 2018;(15):1666-1678
Abstract
AIM: To evaluate the impact of enhanced recovery after surgery (ERAS) programs on postoperative complications of pancreatic surgery. METHODS Computer searches were performed in databases (including PubMed, Cochrane Library and Embase) for randomized controlled trials or case-control studies describing ERAS programs in patients undergoing pancreatic surgery published between January 1995 and August 2017. Two researchers independently evaluated the quality of the studies' extracted data that met the inclusion criteria and performed a meta-analysis using RevMan5.3.5 software. Forest plots, demonstrating the outcomes of the ERAS group vs the control group after pancreatic surgery, and funnel plots were used to evaluate potential publication bias. RESULTS Twenty case-control studies including 3694 patients, published between January 1995 and August 2017, were selected for the meta-analysis. This study included the ERAS group (n = 1886) and the control group (n = 1808), which adopted the traditional perioperative management. Compared to the control group, the ERAS group had lower delayed gastric emptying rates [odds ratio (OR) = 0.58, 95% confidence interval (CI): 0.48-0.72, P < 0.00001], lower postoperative complication rates (OR = 0.57, 95%CI: 0.45-0.72, P < 0.00001), particularly for the mild postoperative complications (Clavien-Dindo I-II) (OR = 0.71, 95%CI: 0.58-0.88, P = 0.002), lower abdominal infection rates (OR = 0.70, 95%CI: 0.54-0.90, P = 0.006), and shorter postoperative length of hospital stay (PLOS) (WMD = -4.45, 95%CI: -5.99 to -2.91, P < 0.00001). However, there were no significant differences in complications, such as, postoperative pancreatic fistulas, moderate to severe complications (Clavien-Dindo III- V), mortality, readmission and unintended reoperation, in both groups. CONCLUSION The perioperative implementation of ERAS programs in pancreatic surgery is safe and effective, can decrease postoperative complication rates, and can promote recovery for patients.
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Surgical Stress Response and Enhanced Recovery after Laparoscopic Surgery - A systematic review.
Crippa, J, Mari, GM, Miranda, A, Costanzi, AT, Maggioni, D
Chirurgia (Bucharest, Romania : 1990). 2018;(4):455-463
Abstract
Background: Enhanced Recovery Program (ERP) is a multimodal perioperative protocol. Its feasibility and benefits on short term outcomes have been widely reported. These well described improvements, like shorter length of stay and early resumption of body's functions, represent the consequence of an attenuated surgical stress response (SSR). When this response is uncontrolled, it leads to postoperative complications and poor long-term outcomes. SSR can be easily monitored through the analyses of mediators in the bloodstream. Available evidences do not achieve to tell if ERP allows a measurable surgical stress reduction. In this review, we searched for papers investigating the surgical stress response and ERP applied to elective mini-invasive procedures, in order to better understand the level of evidence regarding the effectiveness of ERP in minimizing the surgical stress response. Materials and Methods: A systematic review of published literature was performed using PubMed, Cochrane, EMBASE and Google Scholar database, following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Included studies concerned SSR analysis in ERP patients undergoing laparoscopic surgery through different surgical specialties. Eight studies with a total of 632 patients were included. Results: The three steps of SSR, endocrine, inflammatory and nutritional were all reported in the papers included in this review. Results showed no powerful evidence of difference in endocrine phase while an attenuated inflammatory response was reported for ERP patients when Interleukin-6 (IL-6) and C Reactive Protein (CRP) were dosed. Nutritional status was also preserved as albumin, pre-albumin and transferrin had better values in these patients. Conclusions: ERP applied to different types of laparoscopic surgery has a role in reducing SSR. This can be shown by the analysis of mediators such as IL-6, CRP and nutritional markers.