Risk factors for postoperative ileus in hysterectomy: A systematic review and meta-analysis.

Postoperative ileus (POI) refers to the temporary interruption of postoperative gastrointestinal dynamics. Its pathogenesis includes over-activation of sympathetic nervous system, intestinal inflammatory response and surgical trauma, etc. [ 1 ]. The main symptoms are oral feeding intolerance, nausea, vomiting, abdominal pain and distension, delayed defecation and flatus, etc. [ 2 ]. POI is most common in abdominal surgery, especially those involving direct operation of the intestine, which has been extensively researched [ 3 ]. In abdominal surgery, benign disease hysterectomy is the most common gynecological surgery in the world. POI occurs in about 2% of patients after hysterectomy and is one of the most severe subtypes of POI [ 4 ]. Statistics show that more than 600,000 hysterectomies are performed every year [ 5 ]. 33% of women in the United States have had a hysterectomy before the age of 60 [ 5 ]. Therefore, there may be thousands of people who may develop POI after hysterectomy [ 6 – 8 ]. When this happens, increasing the patient’s hospital stay by an average of 3.7 days, and estimated medical costs for POI range from $750 million to $1 billion per year, undoubtedly increasing the burden on medical care and families [ 9 ]. Therefore, understanding related risk factors is of guiding value for understanding POI and accelerating surgical rehabilitation of patients after hysterectomy. Not only that, it can help to develop targeted interventions to reduce the incidence of POI and reduce the medical and family burden. At present, there are some controversies on the risk factors of POI at home and abroad, the pathogenesis of POI and the effective preventive measures are not clear. Therefore, this study conducted a meta-analysis of the risk factors of POI in patients undergoing hysterectomy, summarized the risk factors, and promptly prevented the occurrence of POI and took intervention measures.

Firstly, as far as we know, so far, this is the first systematic review and meta-analysis to focus on factors associated with POI in hysterectomy. Secondly, we conducted an extensive literature search, thoroughly screening research papers, as well as other relevant literature, to minimize the possibility of missing any research. Thirdly, most of the included studies were of high quality with reliable results. However, our view also had some limitations. First of all, there are relatively few studies on the risk factors of POI in hysterectomy patients, so the number of literatures included in the meta-analysis was too small to conduct subgroup analysis for risk factors with large heterogeneity. Therefore, it is suggested to carry out a large number of multi-center, large-sample and high-quality studies to unify the diagnostic criteria of POI and further clarify the risk factors, so as to provide practical and reliable basis for clinical medical staff to manage POI and reduce the incidence of POI. Secondly, due to the limitation of the original literature data, the risk factors closely related to POI, such as uterine pathology and concomitant radiotherapy could not be analyzed in this study. Thirdly, the literatures included in this study were observational studies, which could not determine the exact causal relationship between the POI and its risk factors.

We identified 1644 articles in the initial search of the literature and additional records through other sources. Then, by removing duplicates, screening title abstract and full text, we finally included 11 articles [ 7 , 15 – 24 ]. The detailed selection process is presented in Fig 1 . Most of the analyzed studies were retrospective cohort studies (n = 7). Most of the studies were conducted in USA (n = 5), 3 in China, the others are in France, Canada and Japan, respectively. A total of 59808 patients who underwent hysterectomy from 1994 to 2023 were included in these studies, of whom 758 developed POI (1.3%). Two of the studies included cases of hysterectomy with malignant and benign indications, seven studies with benign indications of hysterectomy and two studies with malignant indications of hysterectomy. The six studies included in meta-analysis were all evaluated for hysterectomy [ 7 , 15 – 19 ]. POI was defined differently among the studies included in the meta-analysis. Five studies defined POI as inability to tolerate oral administration for at least 2 days after surgical intervention, accompanied by nausea, vomiting, abdominal pain, and abdominal distention [ 7 , 15 – 17 , 19 ]. One study did not clearly identify the specific number of days to diagnose POI, relying instead on and radiological characteristics [ 18 ] ( Table 1 ). a RC: retrospective cohort, CC: case–control study, CS: cross-sectional study b Criteria for POI diagnosis: ①Feeding intolerance, nausea, vomiting, abdominal pain and bloating, delayed defecation and flatulence 2 days or more after surgery; ②Radiographically or surgically. Meet one of the above criteria. c Risk factors: 1.Operation approach (laparoscopic/vaginal hysterectomy); 2.Bowel injury; 3.Malignant uterine pathology; 4.Anesthesia technique (general anesthesia); 5.Adhesiolysis; 6.Duration of operation; 7.Previous cancer; 8.Dysmenorrhea; 9.Wound size > 3; 10.Perioperative transfusion; 11.Nonwhite race; 12.Age; 13.Prior abdominal or pelvic surgery; 14.Uterine weight > 250g; 15.No IMRT (Intensity Modulated Radiation Therapy); 16.Body mass index (BMI); 17.Concomitant bowel surgery; 18.Perioperative complications: cystotomy; 19.Smoking; 20.Diabetes; 21.Endometriosis; 22.Use opioids; 23.Concomitant radiotherapy; 24.Paraaortic lymph node dissection (PAND); 25.Hypertension; 26.Dyspnea; 27.Chronic obstructive pulmonary disease (COPD); 28.Coagulopathy; 29.Steroid use; 30.Postmenopausal status. The NOS was used for the 7 cohort studies and 2 case-control studies. The articles included all scored 7–9, which is considered moderate to high quality. The JBI critical appraisal checklist was used to assess the quality of the 2 cross-sectional studies. Both studies satisfy all items. The quality assessment is shown in Figs 2 – 4 , respectively. There are twelve influenced factors for POI in hysterectomy patients included in this study. They can be classified as personal factors and previous history of disease and surgery-related factors. The heterogeneity test and meta-analysis results of each influencing factor were shown below. By analyzing the included articles, five personal factors and history of disease factors were assessed, including use opioids, dysmenorrhea, smoking, prior abdominal or pelvic surgery and age. Sort by the size of the OR value. Meta-analyses demonstrated that use opioids (2 studies, OR = 3.91, 95%CI: 1.08–14.24, S1 Fig), dysmenorrhea (3 studies, OR = 2.51, 95%: 1.25–5.05, S2 Fig), smoking (3 studies, OR = 1.55, 95%: 1.18–2.02, S3 Fig), prior abdominal or pelvic surgery (3 studies, OR = 1.46, 95%CI: 1.16–1.83, S4 Fig) and age (3 studies, OR = 1.03, 95%: 1.02–1.04, S5 Fig) were independent associated factors of sarcopenia ( Table 2 ). Notes: OR: odds ratio, CI:.confidence interval. There were 7 surgery-related factors were assessed in the studies included in the review, including perioperative transfusion, concomitant bowel surgery, anesthesia technique (general anesthesia), adhesiolysis, duration of operation, operation approach (laparoscopic hysterectomy) and operation approach (vaginal hysterectomy). Sort by the size of the OR value. Meta-analyses showed that perioperative transfusion (2 studies, OR = 4.50, 95%CI: 3.29–6.16, S6 Fig), concomitant bowel surgery (2 studies, OR = 3.79, 95%CI: 1.86–7.71, S7 Fig), anesthesia technique (2 studies, general anesthesia) (OR = 2.73, 95%CI: 1.60–4.66, S8 Fig), adhesiolysis (6 studies, OR = 1.97, 95%CI: 1.52–2.56, S9 Fig), duration of operation (2 studies, OR = 1.78, 95%CI: 1.32–2.40, S10 Fig), operation approach (laparoscopic hysterectomy) (2 studies, OR = 0.43, 95%CI: 0.29–0.64, S11 Fig) and operation approach (vaginal hysterectomy) (2 studies, OR = 0.35, 95%CI: 0.18–0.69, S11 Fig) were independent associated factors of sarcopenia ( Table 2 ). Multiple conditions evaluated in our meta-analysis did not reach statistical significance and cannot be considered risk factors for POI. These included BMI, which was assessed in 3 studies and found no significant association between elevated BMI and POI (OR = 1.00, 95%CI: 0.98–1.01, S12 Fig) [ 7 , 17 , 18 ]. Similar findings were found for diabetes (2 studies [ 7 , 18 ], OR = 1.25, 95%CI: 0.88–1.80, S13 Fig), endometriosis (2 studies [ 7 , 17 ], OR = 1.20, 95%CI: 0.87–1.66, S14 Fig) and nonwhite race (2 studies [ 7 , 17 ], OR = 1.35, 95%CI: 0.62–2.95, S15 Fig). Due to the small number of articles included in this paper, publication bias and sensitivity analysis were only performed for risk factors with relatively large number of included articles. As shown in the Fig 5 , the funnel plot is symmetrical, so no publication bias is observed. As shown in the Fig 6 , the combined results of the remaining studies are still meaningful after the literature is eliminated one by one, indicating that the analysis results are not easy to change significantly due to changes in the number of studies, and have a certain degree of robustness.

In summary, this study found that use opioids, dysmenorrhea, smoking, prior abdominal or pelvic surgery, age, perioperative transfusion, concomitant bowel surgery, anesthesia technique (general anesthesia), adhesiolysis, duration of operation, Operation approach (laparoscopic hysterectomy) and operation approach (vaginal hysterectomy) were influenced factors for POI in patients undergoing hysterectomy. This suggests that medical staff should fully assess the patient’s condition, reduce the stimulation of the patient’s intestinal wall during the operation, and nurses and physicians should closely cooperate to control the operation time as much as possible. After the operation, encourage and assist patients to get out of bed early and promote the recovery of gastrointestinal function. Our findings provide a basis for screening high-risk groups for POI, provide a reference for perioperative decision-making, and help reduce the incidence of POI and the resulting medical and family burden. However, further studies are needed to further elucidate the unexplored risk factors for POI, such as BMI, diabetes, endometriosis, uterine pathology, concomitant radiotherapy and so on.

This systematic review was registered in the International Prospective Register of Systematic Reviews (CRD42023407167). The review protocol of this study could also be accessed on it. And this article was conducted under the guidance of the Preferred Reporting Program for Systematic Review and Meta-analysis, Cochrane Meta-analysis and systematic reviews and the Meta-analysis of Observational Studies in Epidemiology guidelines [ 10 – 12 ]. The authors conducted a comprehensive literature search using PubMed, Web of Science, Embase, the Cochrane Library and China National Knowledge Internet. The search period was restricted from the earliest records to March 2024. Exact search terms used on each database (and each platform) are provided in S1 Table . Databases were searched separately, as opposed to multiple databases being searched simultaneously on the same platform. The search results of electronic data base were exported to Endnote X9 software. Results were deduplicated using Endnote software. Two authors (ZH and TL) screened titles and abstracts generated by the search independently and then assessed the full texts of all relevant articles against the inclusion criteria. In case of disagreements, a senior author (QS) was consulted. The inclusion criteria were as follows: The subjects were patients over 18 years of age who underwent elective hysterectomy. The contents of articles included the influencing factors and risk factors of POI in hysterectomy, and the results were converted to odds ratio (OR) values, 95% confidence interval (CI) and standard error (SE). Demonstrate clear criteria for POI diagnosis, and at least one of the following diagnostic criteria is met: ①Feeding intolerance, nausea, vomiting, abdominal pain and bloating, delayed defecation and flatulence 2 days or more after surgery; ②Radiography confirms the diagnosis of POI. The study design should be observational study. The exclusion criteria were as follows: Repeated publication or incomplete literature. The data extraction could not be carried out or the data extraction did not meet the research requirements. Literature review, systematic review, animal experiments, case reports. The POI have been the result of an intra-abdominal complication. We used the definition of POI from the previous original study, which consisted of both symptomatic evaluation and radiologic diagnosis, as described in the previous section on inclusion criteria. Additionally, risk factors for POI were defined as factors identified or suspected to increase the risk of POI during the patient’s perioperative period. These variables need to be significant, as well as at least be considered risk factors in the bivariate analysis. These factors could be secondary outcomes in the literature included in this study, not necessarily primary outcomes. Pre-designed data extraction table was used to extract data independently and cross-check. The data included the following variables: first author, year of publication, country, study design, surgical type, time to POI, sample, POI patients, risk factor. Discrepancies were resolved by consensus. Newcastle-Ottawa scale (NOS) was used to evaluate the quality of the included literature, which included two scales, case-control study and cohort study [ 13 ]. The two scales each contained 3 dimensions and a total of 8 items. The full score of the two scales were 9, and a score of 4–6 for medium quality literature and a score of 7–9 for high quality literature were included in the study [ 13 ]. For cross-sectional studies, we used Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional studies [ 14 ]. The list has eight evaluation items, each corresponding to four answers: not applicable, unclear, no or yes. The higher the number of "yes" answers, the higher the quality of the study. The data were analyzed by Stata17 software, and the OR values of the original data in the literature and 95%CI were used as the combined effect size. I 2 value was used to analyze the heterogeneity. If P > 0.1 and I 2 ≤ 50%, there was no statistical heterogeneity among the studies, the fixed-effects model was used to analyze the heterogeneity. If P ≤ 0.1 and I 2 > 50%, the heterogeneity among studies was high, the random-effects model was used for analysis. The pooled estimates were presented with forest plots. Sensitivity analysis was conducted by using the method of article-by-article exclusion to observe whether there was a significant change in heterogeneity after the exclusion of references, and to observe the change of the OR value. If heterogeneity changed significantly after the exclusion of each paper, the paper might be the source of heterogeneity, and analyze why it became the source of heterogeneity. Alternatively, sensitivity analysis could be performed by changing the merge model. If the combined results of fixed-effects model and random-effects model are inconsistent, it meant instability. The funnel plot was used to analyze publication bias for variables with more than 10 included literatures. If the funnel plot was symmetrical on both sides, it indicated that the possibility of publication bias was small; otherwise, it indicated that the possibility of publication bias was large. P < 0.05 was considered statistically significant.

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