Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-05T13:11:00.878Z Has data issue: false hasContentIssue false

Impact of total parenteral nutrition v. exclusive enteral nutrition on postoperative adverse outcomes in patients with penetrating Crohn’s disease undergoing surgical resection: a retrospective cohort study

Published online by Cambridge University Press:  04 June 2024

Zhenya Sun
Affiliation:
Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, People’s Republic of China
Lei Cao
Affiliation:
Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, People’s Republic of China
Yusheng Chen
Affiliation:
Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, People’s Republic of China
Tianrun Song
Affiliation:
Department of General Surgery, Jinling Clinical School of Medicine (Eastern Theater General Hospital), Nanjing Medical University, Nanjing 210002, People’s Republic of China
Zhen Guo
Affiliation:
Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, People’s Republic of China
Weiming Zhu
Affiliation:
IBD Therapeutic Center, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
Yi Li*
Affiliation:
Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, People’s Republic of China
*
*Corresponding author: Dr Yi Li, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Achieving optimal nutritional status in patients with penetrating Crohn’s disease is crucial in preparing for surgical resection. However, there is a dearth of literature comparing the efficacy of total parenteral nutrition (TPN) v. exclusive enteral nutrition (EEN) in optimising postoperative outcomes. Hence, we conducted a case-matched study to assess the impact of preoperative EEN v. TPN on the incidence of postoperative adverse outcomes, encompassing overall postoperative morbidity and stoma formation, among penetrating Crohn’s disease patients undergoing bowel surgery. From 1 December 2012 to 1 December 2021, a retrospective study was conducted at a tertiary centre to enrol consecutive patients with penetrating Crohn’s disease who underwent surgical resection. Propensity score matching was utilised to compare the incidence of postoperative adverse outcomes. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with adverse outcomes. The study included 510 patients meeting the criteria. Among them, 101 patients in the TPN group showed significant improvements in laboratory indicators at the time of surgery compared with pre-optimisation levels. After matching, TPN increased the occurrence of postoperative adverse outcomes (92·2 % v. 64·1 %, P = 0·001) when compared with the EEN group. In the multivariate analysis, TPN showed a significantly higher OR for adverse outcomes than EEN (OR = 4·241; 95 % CI 1·567–11·478; P = 0·004). The study revealed that penetrating Crohn’s disease patients who were able to fulfil their nutritional requirements through EEN exhibited superior nutritional and surgical outcomes in comparison with those who received TPN.

Type
Research Article
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

Crohn’s disease (CD) is a chronic, transmural inflammatory disease that can affect any part of the gastrointestinal tract, from the mouth to the anus. Repeated episodes of active inflammation in the intestinal lumen can lead to serious complications, such as strictures and perforation of the intestinal wall(Reference Cushing and Higgins1). Penetrating CD can present as phlegmons, abscesses or fistulas(Reference Hirten, Shah and Sachar2). The penetrating nature of the disease can lead to the malnutrition status and inflammatory response which are associated with postoperative morbidity(Reference Kanazawa, Yamana and Okamoto3,Reference Huang, Tang and Nong4) . Thereafter, prehabilitation or preoperative optimisation, which involves interventions such as antibiotics, percutaneous drainage and nutrition support, plays a crucial role in the management of patients with CD who are undergoing surgical resection(Reference Hirten, Shah and Sachar2,Reference Papa, Lopetuso and Minordi5) . Optimisation of nutritional status is essential in the initial management of penetrating CD, as it prepares the patient for surgical resection if needed.

Exclusive enteral nutrition (EEN) can promote mucosal healing, correct nutritional imbalances and minimise disease activity in patients with inflammatory bowel disease(Reference Wall, Day and Gearry6Reference Pigneur, Lepage and Mondot8). The European Society for Clinical Nutrition and Metabolism guidelines recommend using enteral nutrition (EN) formulas or liquids over parenteral nutrition (PN) unless EN is completely contraindicated. PN should only be used as the sole intervention in cases where EN is impossible, especially in the surgical management of nutrition in inflammatory bowel disease. Contraindications to EEN include intestinal obstruction or ileus, severe shock, intestinal ischaemia, high output fistula and severe intestinal haemorrhage(Reference Bischoff, Bager and Escher9). Preoperative nutrition therapy is demonstrated to be effective in decreasing postoperative complications and the reduced rate of stoma creation(Reference Wang, Zuo and Zhao10). Enteral nutrition before surgery is also found to be associated with the shorter length of resected bowel(Reference Meade, Patel and Luber11).

Despite the potential benefits of EEN, there is a lack of literature comparing the differences between total parenteral and exclusive enteral nutrition optimisation on postoperative complications. Therefore, we conducted a case-matched study to assess the impact of preoperative EEN v. total parenteral nutrition (TPN) on the incidence of complications in patients undergoing bowel surgery for penetrating CD, while considering potential variables that may influence the development of postoperative complications. We hypothesise that patients with penetrating CD receiving preoperative TPN have increased postoperative adverse outcomes compared with those receiving EEN.

Method

Patients and data collection

Between 1 December 2012 and 1 December 2021, we enrolled all consecutive patients with penetrating CD who underwent surgery at a tertiary inflammatory bowel disease centre. Penetrating CD was defined as CD imaging showing abdominal abscess, phlegmon or intra- or extra-intestinal fistula(Reference Peyser, Carmichael and Dean12). The diagnosis of penetrating CD was established based on symptoms and conventional imaging modalities, including computed tomography, MRI or abdominal ultrasound. Patients with perianal fistulae/abscess without abdominal/pelvic abscess/fistulae were excluded from the study. Additionally, we excluded patients who underwent emergency surgery or received preoperative partial EN plus PN.

We collected various data including demographics, disease location according to the Montreal classification, smoking status, preoperative medications, history of previous CD bowel resection, preoperative laboratory test results, type of surgery, use of laparoscopic or open access, operative time, operative blood loss, creation of primary anastomosis or diversion stoma and postoperative outcomes. Propensity score matching was employed to minimise potential selection bias and compare the effect of EEN v. TPN, considering all covariates that may influence the management of preoperative nutritional status. Matching was performed using a 1:3 ‘nearest neighbour’ calliper = 0·02, case–control match without replacement, based on several factors, including upper gastrointestinal lesion, type of penetrating lesion and type of surgery. This study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving patients were approved by the Ethics Committee of Jinling Hospital (no. 2022DZKY-048-01).

Total parenteral nutrition and exclusive enteral nutrition groups

Our exposure of interest was TPN, defined as patients who had received TPN for a minimum of 7 consecutive d before surgery and were subsequently included in the study(Reference Braga, Ljungqvist and Soeters13,Reference Ayoub, Kamel and Ouni14) . The decision to initiate TPN was based on the patient’s characteristics and contraindication to EN, as determined by the colorectal surgeon and nutritionist. Patients received a personalised TPN formula through either a central venous catheter or peripherally inserted central catheter. Macronutrient dosages were based on the patient’s body weight, with 1·2–1·5 g/kg of amino acids, 2 mg/kg per min of 70 % dextrose and 250–500 ml of lipids. A specialist parenteral nutrition pharmacist made daily micronutrient and electrolyte adjustments tailored to the individual needs of the patient.

The comparator was EN, defined as patients who received EEN for at least 2 weeks before surgery, with a normal diet excluded(Reference Bischoff, Bager and Escher9,Reference Meade, Patel and Luber11,Reference Heerasing, Thompson and Hendy15) . Preoperative EEN in penetrating CD is routinely administered via nasogastric or nasointestinal tube using an infusion pump. Nutritional requirements are calculated according to the guidelines of the parenteral and enteral nutrition team manual(16), with a target range of 25–35 kcal/kg per d and a maximum increase of 500 kcal/d in cases of malnutrition. One or more of the following products was prescribed for use: Enteral Nutritional Emulsion (TP)® and Enteral Nutritional Emulsion (TP-HE)® (Fresenius Kabi, China); Enteral Nutritional Suspension (TP-MCT)®, Enteral Nutritional Suspension (TPF)®, Peptisorb Liquid® and Nutrison® (Nutricia, China); and ENSURE® (Abbott Nutrition, China).

Outcome

Our primary outcome was the incidence of postoperative adverse outcomes, comprising overall postoperative morbidity and stoma formation. The overall postoperative morbidity referred to any complications within 30 d after surgery. We categorised postoperative complications as superficial wound infection, ileus, anastomotic bleeding, abdominal bleeding, septicaemia, pneumonia, urinary infection, catheter infection, reoperation, severe postoperative complications, intra-abdominal septic complications, surgical site infection, infectious complications and overall morbidity. We defined ileus as the inability to tolerate oral food for more than 5 d in the absence of clinical and imaging evidence of mechanical obstruction(Reference Rychter and Clavé17). Severe postoperative complications were those with a grade >2 according to the Clavien–Dindo classification(Reference Dindo, Demartines and Clavien18). Intra-abdominal septic complications were defined as peritonitis, abscess or anastomotic leak. Surgical site infection encompassed intra-abdominal septic complications, wound infection or wound dehiscence(Reference Syed, Cross and Flasar19). Infectious complications included all infectious complications such as surgical site infection, septicaemia, pneumonia, urinary infection and catheter infection. We also collected the length of postoperative hospital stay and requirement for temporary stoma.

Statistical analysis

Categorical variables were compared using frequency counts and either the χ 2 or Fisher’s exact test, depending on appropriateness. Continuous variables were reported as means and sd or medians and interquartile ranges (IQR), based on normality, and compared using ANOVA or Kruskal–Wallis tests, as appropriate. Paired t tests and Wilcoxon signed-rank tests were utilised to compare laboratory indicators of TPN before and after treatment. All variables associated with a P value of less than 0·1 were subsequently included in a binary logistic regression model. Statistical significance was defined as a P value of less than 0·05. We conducted statistical analyses using R version 4·2·3 (R Foundation for Statistical Computing, Vienna, Austria), along with the MatchIt package, and analysed data using IBM SPSS version 21. The total sample size was determined using G*Power version 3·1·9·7 for logistic regression analysis, with an OR of 3·47, a significance level (α) set at 0·05 and a statistical power of 0·95. This calculation yielded a total sample size of 424 participants.

Results

Patient characteristics

This study is a retrospective cohort study that enrolled 660 patients with penetrating CD who underwent surgery. Among them, 510 patients met the inclusion criteria, while the remaining patients were excluded for various reasons. Specifically, twenty-two patients lacked clinical data, thirty patients received partial EN plus PN, and ninety-eight patients underwent emergency surgery. Consequently, 409 cases in the EN group and 101 cases in the PN group were subjected to propensity score matching analysis (Fig. 1).

Fig. 1. Flow chart of the study. CD, Crohn’s disease; EEN, exclusive enteral nutrition; TPN, total parenteral nutrition.

Table 1 displays the baseline characteristics of the 510 patients. Analysis of the data revealed significant differences in clinical characteristics and surgical procedures between the two groups. The EEN group had a significantly higher frequency of enterocutaneous fistula compared with the TPN group (P = 0·001). In contrast, the TPN group had a significantly higher frequency of abscess and internal fistula presence compared with the EEN group (P = 0·009 and P = 0·043, respectively). Additionally, the EEN group had a significantly lower frequency of small bowel resection compared with the TPN group (P = 0·02), whereas the frequency of ileocolectomy was significantly higher in the EEN group compared with the TPN group (P = 0·002). It is worth noting that the differences in the frequency of upper gastrointestinal lesions, phlegmon and segmental colectomy between the two groups did not reach statistical significance (P = 0·088, P = 0·087, P = 0·093, respectively).

Table 1. Outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative total parenteral nutrition (TPN) group before propensity score matching

IQR, interquartile range; CD, Crohn’s disease; CRP, C-reactive protein.

Total parenteral nutrition and exclusive enteral nutrition composition characteristics

Overall, the mean daily protein intake for patients receiving TPN was 100 g (range 75–100), corresponding to an average protein intake of 2·1 g/kg of body weight (range 1·8–2·4). The mean amount of dextrose administered per d was 150 g (range 150–175), equivalent to a mean intake of 3·3 g/kg of body weight (range 2·9–4·1). In terms of lipid administration, there was a mean of 50 g (range 50–60), resulting in a mean intake of 1·17 g/kg of body weight (range 1·02–1·32). On average, the TPN formula provided a mean of 1450 calories per d (range 1445–1612), corresponding to a mean energy intake of 32·2 kJ/kg of body weight (range 29·1–37·8). Conversely, the EEN formula supplied a mean of 1500 calories per d (range 1500–2000), which equated to a mean of 33·3 kJ/kg of body weight (range 28·8–40·0). The mean daily protein intake for patients receiving EEN was 64 g (range 60–80), representing a mean intake of 1·3 g/kg of body weight (range 1·1–1·6). The average daily lipid intake for patients undergoing EEN was 34 g (range 25·5–63·9). Enteral nutrition lipids encompass different varieties, including long-chain TAG, medium-chain TAG and n-3. On the other hand, parenteral nutrition lipids consist of various types, such as long-chain TAG, medium-chain TAG, fish oil-based emulsions and structured lipids.

Preoperative nutritional optimisation

Table 2 presents the distribution of different contraindications to EEN in the TPN population. Obstructed bowel is the most prevalent condition, accounting for 39·6 % of all cases, followed by internal fistula observed in 33·7 % of cases and gut dysfunction present in 18·8 % of cases. The remaining cases are divided between abscess and high output fistula, with a prevalence of 5·9 and 2·0 %, respectively.

Table 2. Indications of total parenteral nutrition

All 101 patients in the TPN group exhibited significant improvements in albumin and Hb following TPN pre-optimisation compared with baseline levels. The changes in parameters are shown in online Supplementary Fig. 1. Meanwhile, the data presented in Table 1 revealed statistically significant differences between the TPN and EEN groups across multiple variables. Specifically, individuals in the EEN group exhibited significantly higher mean BMI values compared with those in the TPN group (P = 0·001). Furthermore, the EEN group showed significantly higher mean Hb levels (P = 0·001) and mean albumin levels (P = 0·001) compared with the TPN group. Additionally, individuals in the EEN group displayed significantly lower mean C-reactive protein (CRP) levels than those in the TPN group (P = 0·001). Moreover, the EEN group demonstrated a significantly lower Crohn′s disease activity index (CDAI) mean score (182·8 ± 33·6) when compared with the TPN group (323·4 ± 33·8), with a P value of 0·001. The EEN group also exhibited a significantly lower weight loss rate (36·2 %) in contrast to the TPN group (61·4 %), with a P value of 0·001. Furthermore, the pre-surgery weight was significantly higher in the EEN group (50 kg (IQR 45–57)) as opposed to the TPN group (45 kg (IQR 40–51)), with a P value of 0·001.

Postoperative outcomes

Table 3 presents a comparison of postoperative outcomes between two groups of patients who underwent surgery: those who received EN (EEN group) and those who received TPN (TPN group). The EEN group had a lower incidence of abdominal bleeding (0·5 % v. 3·0 %, P = 0·056) and catheter infection (0·5 % v. 6·9 %, P = 0·001) compared with the TPN group. However, there were no significant differences between the two groups in the incidence of ileus, superficial wound infection, intra-abdominal septic complications, surgical site infection, anastomotic bleeding, septicaemia, pneumonia, urinary infection, infectious complications, severe postoperative complications and overall postoperative morbidity. Additionally, there was no significant difference between the two groups in terms of the length of postoperative hospital stay. The median postoperative hospital stay was 9 d for the EEN group and 10 d for the TPN group (P = 0·227).

Table 3. Comparison of postoperative outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative total parenteral nutrition (TPN) group before propensity score matching

IQR, interquartile range.

Propensity score matching

Following a 1:3 propensity score matching, 90 patients were included in the TPN group and 223 in the EEN group. The incidence of upper gastrointestinal lesions was comparable between the TPN and EEN groups (14·4 % v. 11·2 %, respectively, P = 0·428), as well as the type of penetrating lesions and type of surgery, as shown in Table 4. Additionally, there were no significant differences in age, sex, disease duration, Montreal classification, smoking habits, surgical history and preoperative medication between the two groups.

Table 4. Outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative (total parenteral nutrition) TPN group after propensity score matching

IQR, interquartile range; CD, Crohn’s disease; CRP, C-reactive protein.

Preoperative prehabilitation outcomes after Propensity Score Matching (PSM)

Table 4 displays the preoperative prehabilitation outcomes for two groups of patients who underwent PMS, comparing BMI, Hb levels, albumin levels and CRP levels. The results indicate that the EEN group had a higher median BMI, Hb levels and albumin levels and a lower median CRP level compared with the TPN group. In addition, the P values for the differences between the two groups were all statistically significant (P < 0·001).

Postoperative outcomes after PSM

After PMS, the study found that the laparoscopic approach was utilised more frequently in the EEN group compared with the TPN group (20·6 % v. 5·6 %, P = 0·001). On the other hand, stomas were more commonly created in the TPN group (81·1 %) than in the EEN group (37·2 %, P = 0·001).

Regarding postoperative complications, there were no significant differences between the two groups in most aspects. However, the EEN group exhibited a lower overall postoperative morbidity rate than the TPN group (44·8 % v. 57·8 %, P = 0·038). Additionally, a statistically significant difference was observed between the groups in terms of postoperative catheter infection, with the TPN group having a higher incidence of catheter infection than the EEN group (7·8 % v. 0·9 %, P = 0·003). Although the TPN group had slightly higher rates of surgical site infection and infectious complications, these differences did not reach statistical significance (refer to Table 5).

Table 5. Comparison of postoperative outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative total parenteral nutrition (TPN) group after propensity score matching

IQR, interquartile range.

Adverse outcomes and their risk factors

Both univariate and multivariate analyses were conducted to assess potential factors associated with postoperative adverse outcomes after propensity score matching. In the univariate analysis, several factors demonstrated significant associations with adverse outcomes. These factors included disease location (L3 v. L1), BMI, Hb level, albumin level, CRP level, operative blood loss, operative time, surgical approach, small bowel resection and segmental colectomy.

In the multivariate logistic regression models, first, L3 disease location relative to L1 was found to be significantly associated with adverse outcomes (P = 0·033; OR = 2·466; 95 % CI 1·074–5·661). Second, CRP level exhibited a significant association with adverse outcomes (p = 0·009; OR = 1·033; 95 % CI 1·008–1·058). Moreover, independent risk factors of adverse outcomes included operative blood loss (P = 0·001; OR = 1·009; 95 % CI 1·004–1·013) and operative time (P = 0·035; OR = 1·009; 95 % CI 1·001–1·017). Lastly, the multivariate analysis indicated that patients receiving TPN had a significantly higher OR of adverse outcomes compared with those receiving EEN (OR = 4·241; 95 % CI 1·567–11·478; P = 0·004) (Table 6).

Table 6. Univariate and multivariate analysis of risk factors for adverse outcomes after propensity score matching

CD, Crohn’s disease; TPN, total parenteral nutrition; EEN, exclusive enteral nutrition; CRP, C-reactive protein.

Discussion

The objective of this study was to compare surgical outcomes in two groups of patients with penetrating CD: 101 patients who received preoperative TPN optimisation and 409 patients who received preoperative EEN optimisation. The study found that patients who received TPN demonstrated significantly higher serum albumin and Hb levels at the time of surgery compared with pre-optimisation levels. After performing propensity score matching, our data showed that preoperative pre-rehabilitation outcomes were better in the EEN group compared with the TPN group. Specifically, the EEN group had higher BMI, Hb and albumin levels and lower CRP levels, which may indicate better nutritional status and less inflammation. Furthermore, the EEN group exhibited lower rates of postoperative stoma, catheter-related infections and overall complications when compared with the TPN group.

Optimising the nutritional status of patients is crucial in the initial management of penetrating CD, as malnutrition is an independent risk factor for all postoperative complications after abdominal surgery(Reference Jabłońska and Mrowiec20Reference Wobith and Weimann22). According to the guidelines of the American Society for Parenteral and Enteral Nutrition, EN is usually the preferred choice in clinical practice due to its lower incidence of infectious complications and cost-effectiveness(Reference Boullata, Carrera and Harvey23). TPN is reserved for patients who cannot tolerate the energy provided EN. However, there are limitations to the available research on this topic. In this retrospective study, we compared the outcomes of total parenteral and total enteral nutrition for penetrating CD and evaluated their respective impacts on postoperative complications. Our study is the first to compare these two nutritional support methods for this patient population.

Our study revealed a significant increase in preoperative albumin and Hb levels after TPN optimisation compared with before optimisation. Similarly, a recent study demonstrated that exclusive preoperative TPN can significantly enhance nutritional status and prompt clinical and laboratory remission in patients with severe active CD(Reference Zittan, Gralnek and Hatoum24). However, the use of TPN as an alternative to preoperative nutrition has shown mixed benefits among surgical patients. Specifically, preoperative TPN administration has been linked to rapid improvement in nitrogen balance and lymphocyte function recovery(Reference Morlion, Stehle and Wachtler25). Other studies have also reported noteworthy improvements in nutritional indicators after TPN treatment(Reference Evans, Steinhart and Cohen26,Reference Turkot and Sobocki27) . Collectively, these findings suggest that preoperative TPN can lead to significant nutritional enhancement.

EEN has demonstrated therapeutic effects in CD that extend beyond addressing malnutrition and improving nutritional status. The ability of EEN to induce remission and reduce gut inflammation holds potential implications for surgical outcomes in these patients. EEN acts as an induction therapy for CD. Research has consistently shown that EEN leads to improvements in clinical symptoms and promotes mucosal healing in individuals with CD(Reference Fell, Paintin and Arnaud-Battandier28). This is achieved through the modulation of the inflammatory response by EEN, which involves decreasing pro-inflammatory cytokine production and increasing the release of anti-inflammatory mediators(Reference Berntson, Hedlund-Treutiger and Alving29). As a result, EEN effectively attenuates CD activity. Moreover, EEN exerts an influence on the composition of the gut microbiota. This alteration in the microbial balance contributes to the reduction of inflammation and the promotion of mucosal healing(Reference MacLellan, Moore-Connors and Grant30). It is worth noting that one notable advantage of EEN is its excellent tolerability and absence of the adverse effects commonly associated with corticosteroid therapy. Consequently, EEN is considered a favourable treatment option, particularly in children(Reference Yu, Chen and Chen31).

A systematic analysis by Braunschweig et al. compared EN with PN and found that EN was associated with a lower risk of infection but higher mortality rates. In malnourished populations, the risk of infection tends to be higher with conventional oral diets with intravenous dextrose than with PN(Reference Braunschweig, Levy and Sheean32). Elke G et al. found that in critically ill patients, EN had no effect on overall mortality but decreased infectious complications and intensive care unit (ICU) length of stay(Reference Elke, van Zanten and Lemieux33). Mazaki et al.’s meta-analysis confirmed that EN is more beneficial than PN in reducing any complication, any infectious complication, anastomotic leak, intra-abdominal abscess and duration of hospital stay in patients after gastrointestinal surgery(Reference Mazaki and Ebisawa34). Zhao et al.’s meta-analysis of 18 Randomized Controlled Trials (RCTs) with 2540 gastrointestinal cancer patients showed that patients who received EN had a shorter time to flatus, shorter lengths of hospital stay and a greater increase in albumin levels compared with TPN(Reference Zhao, Wu and Zhao35). The superiority of EEN over TPN has been established. One key mechanism that contributes to the potential advantages of EEN compared with TPN is its impact on the gut microbiota. EEN induces favourable changes in the microbial community’s composition, leading to a more diverse and beneficial microbiota(Reference Runde, Veseli and Fogarty36). This modulation of the gut microbiota is believed to be associated with a reduction in inflammation and improved healing of the intestinal lining. Conversely, TPN bypasses the digestive system entirely and does not interact with the gut microbiota. Furthermore, EEN has been shown to effectively regulate pro-inflammatory cytokine production in the gut, resulting in a decrease in these cytokines’ levels while simultaneously promoting anti-inflammatory mediator release(Reference Melton, Taylor and Gibson37). However, TPN does not exert a direct effect on the gut inflammatory response. Another factor to consider is the potential impact of EEN on the integrity of the gut barrier function. EEN has been observed to enhance the strength of the intestinal barrier, preventing harmful substances and bacteria from entering the bloodstream(Reference Ashton, Gavin and Beattie38). This preservation of gut barrier function plays a crucial role in reducing inflammation and facilitating the healing of the intestinal mucosa. In contrast, TPN does not have the same influence on gut barrier function. This may also account for the greater weight loss observed in the TPN group compared with the EEN group. TPN delivers nutrients directly into the bloodstream, while EEN involves consuming a liquid formula that provides all necessary nutrients through a feeding tube, facilitating normal physiological processes of digestion and absorption. Additionally, the inflammatory state of the patient may influence weight loss differences. Our findings also indicate a significantly lower mean CDAI score in the EEN group compared with the TPN group. These variations in delivery method and nutrient absorption could contribute to divergent weight loss outcomes. The European Society for Clinical Nutrition and Metabolism 2021 practical guidelines state that PN should be administered as soon as possible if nutrition therapy is indicated and there is a contraindication for EN(Reference Weimann, Braga and Carli39). However, EN should always take precedence over PN. When EN is completely contraindicated, PN is the better option. Our data suggest that TPN can optimise patient nutrition in cases where total EN is contraindicated. However, compared with EEN optimisation, the TPN group showed more severe disease activity and malnutrition at the time of surgery, as well as higher postoperative stoma rates, catheter infection rates and overall complications.

Our study is limited by several factors. The retrospective nature of our study design exposes it to the influence of unmeasured confounding variables. However, we addressed this concern by employing a matching process that enhanced comparability between the two groups in terms of baseline characteristics. As a result, potential bias in the analysis was mitigated. High utilisation of TPN is that it may reflect a population of patients who are more unwell compared with those receiving EEN. It should be noted that the EN group exhibited higher mean BMI, albumin and Hb levels, as well as lower CRP levels compared with the TPN group. These inherent baseline differences render the achievement of our primary objective, which is to directly compare outcomes between TPN and EN, challenging. The inclusion of patients receiving TPN, who typically have more severe diseases, can significantly impact our experimental design and results. This potential bias may lead to a focus on more complex and critical cases in our study cohort, potentially distorting overall outcomes and limiting the generalizability of our findings. Moreover, the heightened severity of illness among TPN patients could influence treatment responses, clinical endpoints and overall study outcomes. Besides, we agree that relying solely on BMI, Hb, albumin and CRP lacks both comprehensiveness and specificity in diagnosing malnutrition or evaluating overall nutritional status. We acknowledge that the absence of more thorough assessments is indeed a limitation in our research, and a more comprehensive evaluation of nutritional status would have yielded valuable insights.

Optimising the nutritional status of patients with penetrating CD is a crucial step prior to surgical resection. According to the guidelines of the European Society for Clinical Nutrition and Metabolism, EEN is the preferred mode of nutritional support for these patients due to its ability to promote intestinal mucosal healing, correct nutritional imbalances and reduce disease activity(Reference Weimann, Braga and Carli40). However, limited literature is available regarding the comparison of TPN and EEN optimisation on postoperative complications. Some studies have suggested that EEN may be associated with a lower risk of postoperative complications compared with TPN(Reference Mazaki and Ebisawa34,Reference O’Hanlon, Sandall and Darakhshan41) . Nevertheless, further research is necessary to confirm these findings and determine the optimal mode of nutritional support for patients with penetrating CD undergoing surgical resection. In this regard, our research highlights the importance of preoperative TPN nutrition optimisation for penetrating CD patients with contraindications to EEN. Our study has demonstrated that patients who were able to meet their nutritional needs through EEN had better nutritional and surgical outcomes when compared with patients who received TPN. However, a prospective cohort study is required to validate these results.

Acknowledgements

I am particularly thankful to Yan Zhou for her assistance that helped shape this research.

The study was approved by the Ethics Committee of Jinling Hospital.

This work was partly supported by the National Natural Science Foundation of China (grant 82170573, 82270543 and 81770556).

Z. S., L. C. and Y. C. contributed equally to this work. Y. L. and W. Z. conceived and designed the study, interpretation of data and revision of content. Z. S., L. C. and Y. C. were involved in the acquisition, interpretation of data and drafting of the manuscript; T. S. and Z. G. were involved in the interpretation of data and revision of content. All authors read and approved the final manuscript.

None of the authors has any conflicts of interest to declare.

The database is available if properly requested and can be directly addressed to the corresponding author’s email address.

Supplementary material

For supplementary material/s referred to in this article, please visit https://doi.org/10.1017/S0007114524001247.

Footnotes

These authors contributed equally to this work.

References

Cushing, K & Higgins, PDR (2021) Management of Crohn disease: a review. JAMA 325, 6980.CrossRefGoogle ScholarPubMed
Hirten, RP, Shah, S, Sachar, DB, et al. (2018) The management of intestinal penetrating Crohn’s disease. Inflamm Bowel Dis 24, 752765.CrossRefGoogle ScholarPubMed
Kanazawa, A, Yamana, T, Okamoto, K, et al. (2012) Risk factors for postoperative intra-abdominal septic complications after bowel resection in patients with Crohn’s disease. Dis Colon Rectum 55, 957962.CrossRefGoogle ScholarPubMed
Huang, W, Tang, Y, Nong, L, et al. (2015) Risk factors for postoperative intra-abdominal septic complications after surgery in Crohn’s disease: a meta-analysis of observational studies. J Crohn’s Colitis 9, 293301.CrossRefGoogle ScholarPubMed
Papa, A, Lopetuso, LR, Minordi, LM, et al. (2020) A modern multidisciplinary approach to the treatment of enterocutaneous fistulas in Crohn’s disease patients. Expert Rev Gastroenterol Hepatol 14, 857865.CrossRefGoogle Scholar
Wall, CL, Day, AS & Gearry, RB (2013) Use of exclusive enteral nutrition in adults with Crohn’s disease: a review. World J Gastroenterol 19, 76527660.CrossRefGoogle ScholarPubMed
Akobeng, AK, Zhang, D, Gordon, M, et al. (2018) Enteral nutrition for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 8, CD005984.Google ScholarPubMed
Pigneur, B, Lepage, P, Mondot, S, et al. (2019) Mucosal healing and bacterial composition in response to enteral nutrition vs steroid-based induction therapy-a randomised prospective clinical trial in children with Crohn’s disease. J Crohn’s Colitis 13, 846855.CrossRefGoogle ScholarPubMed
Bischoff, SC, Bager, P, Escher, J, et al. (2023) ESPEN guideline on clinical nutrition in inflammatory bowel disease. Clin Nutr (Edinburgh, Scotland) 42, 352379.CrossRefGoogle ScholarPubMed
Wang, H, Zuo, L, Zhao, J, et al. (2016) Impact of preoperative exclusive enteral nutrition on postoperative complications and recurrence after bowel resection in patients with active Crohn’s disease. World J Surg 40, 19932000.CrossRefGoogle Scholar
Meade, S, Patel, KV, Luber, RP, et al. (2022) A retrospective cohort study: pre-operative oral enteral nutritional optimisation for Crohn’s disease in a UK tertiary IBD centre. Aliment Pharmacol Ther 56, 646663.CrossRefGoogle Scholar
Peyser, DK, Carmichael, H, Dean, A, et al. (2022) Early versus delayed ileocolic resection for complicated Crohn’s disease: is “cooling off” necessary?. Surg Endosc 36, 42904298.CrossRefGoogle ScholarPubMed
Braga, M, Ljungqvist, O, Soeters, P, et al. (2009) ESPEN guidelines on parenteral nutrition: surgery. Clin Nutr (Edinburgh, Scotland) 28, 378386.CrossRefGoogle ScholarPubMed
Ayoub, F, Kamel, AY, Ouni, A, et al. (2019) Pre-operative total parenteral nutrition improves post-operative outcomes in a subset of Crohn’s disease patients undergoing major abdominal surgery. Gastroenterol Rep 7, 107114.CrossRefGoogle Scholar
Heerasing, N, Thompson, B, Hendy, P, et al. (2017) Exclusive enteral nutrition provides an effective bridge to safer interval elective surgery for adults with Crohn’s disease. Aliment Pharmacol Ther 45, 660669.CrossRefGoogle Scholar
ASPEN Board of Directors and the Clinical Guidelines Task Force (2002) Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenteral Enteral Nutr 26, 1SA138SA.Google Scholar
Rychter, J & Clavé, P (2013) Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets. Gut 62, 15341535.CrossRefGoogle ScholarPubMed
Dindo, D, Demartines, N & Clavien, P-A (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240, 205213.CrossRefGoogle Scholar
Syed, A, Cross, RK & Flasar, MH (2013) Anti-tumor necrosis factor therapy is associated with infections after abdominal surgery in Crohn’s disease patients. Am J Gastroenterology 108, 583593.CrossRefGoogle ScholarPubMed
Jabłońska, B & Mrowiec, S (2023) Nutritional status and its detection in patients with inflammatory bowel diseases. Nutrients 15, 1991.CrossRefGoogle ScholarPubMed
Brajcich, BC, Stigall, K, Walsh, DS, et al. (2022) Preoperative nutritional optimization of the oncology patient: a scoping review. J Am Coll Surg 234, 384394.CrossRefGoogle ScholarPubMed
Wobith, M & Weimann, A (2021) Oral nutritional supplements and enteral nutrition in patients with gastrointestinal surgery. Nutrients 13, 2655.CrossRefGoogle ScholarPubMed
Boullata, JI, Carrera, AL, Harvey, L, et al. (2017) ASPEN safe practices for enteral nutrition therapy [formula: see text]. JPEN J Parenteral Enteral Nutr 41, 15103.CrossRefGoogle ScholarPubMed
Zittan, E, Gralnek, IM, Hatoum, OA, et al. (2020) Preoperative exclusive total parental nutrition is associated with clinical and laboratory remission in severe active Crohn’s disease-a pilot study. Nutrients 12, 1244.CrossRefGoogle ScholarPubMed
Morlion, BJ, Stehle, P, Wachtler, P, et al. (1998) Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg 227, 302308.CrossRefGoogle ScholarPubMed
Evans, JP, Steinhart, AH, Cohen, Z, et al. (2003) Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease. J Gastrointestinal Surg: Official Journal of the Society for Surgery of the Alimentary Tract 7, 562566.CrossRefGoogle ScholarPubMed
Turkot, M & Sobocki, J (2017) Results of home parenteral nutrition in patients with severe inflammatory bowel disease - an alternative for surgery of malnourished patients. Pol Przegl Chir 89, 2328.CrossRefGoogle Scholar
Fell, JM, Paintin, M, Arnaud-Battandier, F, et al. (2000) Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn’s disease. Aliment Pharmacol Ther 14, 281289.CrossRefGoogle Scholar
Berntson, L, Hedlund-Treutiger, I & Alving, K (2016) Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol 34, 941945.Google ScholarPubMed
MacLellan, A, Moore-Connors, J, Grant, S, et al. (2017) The impact of exclusive enteral nutrition (EEN) on the gut microbiome in Crohn’s disease: a review. Nutrients 9, 447.CrossRefGoogle ScholarPubMed
Yu, Y, Chen, K-C & Chen, J (2019) Exclusive enteral nutrition versus corticosteroids for treatment of pediatric Crohn’s disease: a meta-analysis. World J Pediatr: WJP 15, 2636.CrossRefGoogle Scholar
Braunschweig, CL, Levy, P, Sheean, PM, et al. (2001) Enteral compared with parenteral nutrition: a meta-analysis. Am J Clin Nutr 74, 534542.CrossRefGoogle ScholarPubMed
Elke, G, van Zanten, ARH, Lemieux, M, et al. (2016) Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials. Crit Care 20, 117.CrossRefGoogle Scholar
Mazaki, T & Ebisawa, K (2008) Enteral versus parenteral nutrition after gastrointestinal surgery: a systematic review and meta-analysis of randomized controlled trials in the English literature. J Gastrointestinal Surg: Official Journal of the Society for Surgery of the Alimentary Tract 12, 739755.CrossRefGoogle ScholarPubMed
Zhao, X-F, Wu, N, Zhao, G-Q, et al. (2016) Enteral nutrition versus parenteral nutrition after major abdominal surgery in patients with gastrointestinal cancer: a systematic review and meta-analysis. J Invest Med: the Official Publication of the American Federation for Clinical Research 64, 10611074.CrossRefGoogle ScholarPubMed
Runde, J, Veseli, I, Fogarty, EC, et al. (2023) Transient suppression of bacterial populations associated with gut health is critical in success of exclusive enteral nutrition for children with Crohn’s disease. J Crohn’s Colitis 17, 11031113.CrossRefGoogle ScholarPubMed
Melton, SL, Taylor, KM, Gibson, PR, et al. (2023) Review article: mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn’s disease. Aliment Pharmacol Ther 57, 932947.CrossRefGoogle ScholarPubMed
Ashton, JJ, Gavin, J & Beattie, RM (2019) Exclusive enteral nutrition in Crohn’s disease: evidence and practicalities. Clin Nutr (Edinburgh, Scotland) 38, 8089.CrossRefGoogle ScholarPubMed
Weimann, A, Braga, M, Carli, F, et al. (2021) ESPEN practical guideline: clinical nutrition in surgery. Clin Nutr (Edinburgh, Scotland) 40, 47454761.CrossRefGoogle ScholarPubMed
Weimann, A, Braga, M, Carli, F, et al. (2017) ESPEN guideline: clinical nutrition in surgery. Clin Nutr (Edinburgh, Scotland) 36, 623650.CrossRefGoogle ScholarPubMed
O’Hanlon, D, Sandall, A, Darakhshan, A, et al. (2019) P366 A service evaluation of pre-operative nutritional optimisation in patients with Crohn’s disease using exclusive enteral nutrition with or without supplementary parenteral nutrition. J Crohn’s Colitis 13, S288S288.CrossRefGoogle Scholar
Figure 0

Fig. 1. Flow chart of the study. CD, Crohn’s disease; EEN, exclusive enteral nutrition; TPN, total parenteral nutrition.

Figure 1

Table 1. Outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative total parenteral nutrition (TPN) group before propensity score matching

Figure 2

Table 2. Indications of total parenteral nutrition

Figure 3

Table 3. Comparison of postoperative outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative total parenteral nutrition (TPN) group before propensity score matching

Figure 4

Table 4. Outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative (total parenteral nutrition) TPN group after propensity score matching

Figure 5

Table 5. Comparison of postoperative outcomes of preoperative exclusive enteral nutrition (EEN) group and preoperative total parenteral nutrition (TPN) group after propensity score matching

Figure 6

Table 6. Univariate and multivariate analysis of risk factors for adverse outcomes after propensity score matching

Supplementary material: File

Sun et al. supplementary material

Sun et al. supplementary material
Download Sun et al. supplementary material(File)
File 378.7 KB