Nutrition in Clinical Practice

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Early Enteral Nutrition Improves Outcomes of Open Abdomen in Gastrointestinal Fistula Patients Complicated With Severe Sepsis Yujie Yuan, Jianan Ren, Guosheng Gu, Jun Chen and Jieshou Li Nutr Clin Pract 2011 26: 688 DOI: 10.1177/0884533611426148 The online version of this article can be found at: http://ncp.sagepub.com/content/26/6/688

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Clinical Research

Early Enteral Nutrition Improves Outcomes of Open Abdomen in Gastrointestinal Fistula Patients Complicated With Severe Sepsis

Nutrition in Clinical Practice Volume 26 Number 6 December 2011 688-694 © 2011 American Society for Parenteral and Enteral Nutrition 10.1177/0884533611426148 http://ncp.sagepub.com hosted at http://online.sagepub.com

Yujie Yuan, MD; Jianan Ren, MD; Guosheng Gu, MD; Jun Chen, MD; and Jieshou Li, MD Financial disclosure: This work was supported by grants from the National Natural Science Foundation of China (30872456) and the Key Talent Foundation of the “135” Project from the Government of Jiangsu Province.

included. Fifty-six (68.3%) patients survived to discharge. Fortyone (50%) patients received SER. EN was initiated within 14 days in 36 patients, with a mean initiation time at 8.3 ± 3.4 days; 46 patients did not start any EN within 14 days (29.9 ± 20.9 days). The mean age, BMI, APACHE II score, and fistula characteristics were similar between groups. The abdominal closure was accomplished more rapidly in patients fed within 14 days (142.8 vs 184.5 days, P = .017), with decreased mortality (11.1% vs 47.8%, P < .001). Conclusions: Nutrition therapy plays an important role in the management of gastrointestinal fistula with severe sepsis. Early EN could be successfully delivered for that population, with improved mortality risk. (Nutr Clin Pract. 2011;26:688-694)

Background: Although nutrition therapy is favorably considered as an assistant therapeutic measure in critical illness, little data evaluate its role in gastrointestinal fistula patients with severe sepsis after an open abdomen. The purpose of this study is to evaluate the role of early nutrition therapy in that population. Methods: This is a retrospective review of patients who underwent open abdomen management for gastrointestinal fistula and severe sepsis from January 2001 to June 2009. Nutrition therapy, fistula, abdominal closure, and demographics were noted. Succus entericus reinfusion (SER) was performed for high-output volume or multiple fistulae. Patients were divided into two groups based on whether enteral nutrition (EN) was initiated within 14 days after admission. Delivery route of nutrients, mortality, complications, and time to abdominal closure were compared among groups. Results: Eighty-two patients were

Keywords:  enteral nutrition fistula; intestinal fistula; abdominal wound closure techniques; abdominal wall; sepsis

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for the critical illness. Open abdomen management and relaparotomy have been put into clinical practice.2 The open abdomen is defined simply as a surgical abdomen with the fascial edges purposefully left unapproximated to manage severe intra-abdominal infection, trauma, and other abdominal emergencies.3 The primary goal of this treatment is to achieve permanent abdominal closure by an early definitive operation after the physiological status of patients has returned to the baseline condition. However, considering that protein catabolism is a signpost of critical illness, nutritional status must be paid close attention prior to a definitive operation after an open abdomen.4 Goal-directed nutritional support to ensure appropriate energy and protein intake has been associated with reduced morbidity and mortality in the critically ill.5,6 Nevertheless, the nutritional management for fistula patients after an open abdomen is another challenging problem. For such population, the route of nutrient delivery may be hard to establish or select.

he management of severe sepsis, which results from gastrointestinal fistula, remains a great challenge after an effective fluid resuscitation. Such sepsis is common, and can be characterized by a dramatic hypermetabolic state and overwhelmed homeostasis. Without effective control measures, this severe disease would cause lean body mass loss, visceral hypoperfusion, poor wound healing, immune compromise, multiple organ dysfunction syndrome, or multiple organ failure.1 Conventional treatments, consisting of source control, abdominal lavage and drainage, antimicrobial therapy, and primary closure of peritoneal cavity, are insufficient

From Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R. China Address correspondence to: Jianan Ren, MD, Department of Surgery, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, P.R. China; e-mail: [email protected]

688

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Nutrition Therapy for Intestinal Fistula After an Open Abdomen / Yuan et al   689

Historically, most of controversies regarding open abdomen management focused on the optimal timing and technique of temporary abdominal closure (TAC). Few investigators have focused on the adequate method of nutrition administration for patients receiving open abdomen treatment. Additionally, very little published data have evaluated the role of nutrition therapy in the management of gastrointestinal fistula patients with severe sepsis after an open abdomen. In theory, early administration of nutrition, either by enteral nutrition (EN) or parenteral nutrition (PN), could promote the wound healing process, with a reduced risk of malnutrition caused by inadequate nutrient supply. However, some authors refused to consider early enteral feeding after an open abdomen based on associated side effects, such as poor hemodynamics and ileus. Actually, the common practice of withholding EN in patients with an open abdomen is not supported by the current available literature.7,8 Moreover, the recommendation on delaying the initiation of PN for up to seven days might lead to severe underfeeding, caloric deficit, and impairment of immune defenses, with increased mortality.5,9 We, therefore, reported our results and evaluated the role of early nutrition therapy in the open abdomen population with gastrointestinal fistula and severe sepsis.

Methods Patient Population The medical records of patients referred to our institute were reviewed. The gastrointestinal fistula database was queried to obtain a list of patients who developed severe sepsis and were admitted to the intensive care unit with open abdomens. Patients with admitting diagnoses involving severe sepsis and aged ≥ 18 years were eligible for inclusion. The study period included patients admitted to our clinic center between January 1999 and June 2009. The patients who died within the first 4 days of the hospital stay were excluded from this study. All enrolled patients were subsequently divided into 2 groups based on the initiation time of EN, categorized as having received EN within 14 days of admission or later, after 14 days of admission. The study protocol was approved by the Jinling Hospital Ethical Subcommittee, with written informed consent obtained from all subjects.

Open Abdomen Management The indications and concrete management of open abdomen were generally consistent with previous studies.10,11 In our clinical practice, open abdomen management was performed in the following special circumstance: (1) failure of abdominal closure after a bedside open abdominal

surgery or surgical drainage and (2) an increased risk of organ failure or abdominal compartment syndrome after an effective debridement and drainage. TAC material, such as skin suture repair alone, 3-L transfusion bag (Jiming Drug Co, Zhejiang Province, China), Dacron Strip (with zipper or not, Mersilene tape, Ethicon, Inc, Somerville, NJ, USA), and Polypropylene mesh (Buddy Co, Halifax, Canada), was selected to achieve abdominal closure after an open abdomen. Afterward, split-thickness skin grafting was utilized to cover the abdominal wound areas once the granulation bed had formed.12 The primary goal of open abdomen management was to perform a definitive operation, consisting of resection of existing fistula sites, restoration of gastrointestinal continuity, and reconstruction of abdominal wall defects.13 At the time of definitive surgical treatment, in all cases, the abdominal wall was dissected free, assisted as needed by componentseparation techniques.14

Nutrition Management During the whole process of treatment, nutrition therapy, including EN and PN (all-in-one PN, Jinling Hospital, Nanjing, China), was given. Trophic feeds of at least 30 kcal/kg/d and 1.5 g of protein/kg/d were granted as initial nutrition support goals, and 2 g of nitrogen per L of intestinal fluid output was considered for nutrient administration.4 The detailed therapeutic strategies, such as the general approach of nutrition, route of delivery, and ingredients of nutrients, varied somewhat by critical illness, tolerance to enteral feeding, stage of surgical intervention, nutrition status, and surgeon preference. To be specific, early enteral feeding was preferred as initial nutrition therapy in all patients except those who deteriorated due to hypotensive shock or severe ileus after an attempt to feed enterally. EN was substituted with PN promptly when aforementioned contradictions emerged. Once the output of intestinal fluid was limited and patients were satisfactorily maintained on enteral feeding, EN was gradually introduced to reach the full feeding. The nutrition regimen before and after fistula excision was kept almost unchanged. Succus entericus reinfusion (SER), outlined by Calicis et al,15 was performed for patients who had proximal small bowel fistula with high-output volume (>500 mL/d) or multiple disseminated orificium fistulae. The output from the proximal stoma was collected with a triple catheterization cannula connected to aspiration pumps at a negative pressure of 150 to 200 millibars. The freshly collected succus entericus was drained into a sterile catheter bag, and reinfused back to the distal limb of the mucus fistula through a Foley catheter at specific rate in accordance with the stoma output. In addition, usually somatostatin (6 mg/d, Serono, Feltham, UK) was infused intravenously to control the

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690   Nutrition in Clinical Practice / Vol. 26, No. 6, December 2011

output of intestinal fluid, followed by subcutaneous administration of human growth hormone (Merck Serono, Feltham, UK; 10 IU/d) for a month. Continuous surgical lavage and drainage, mechanical ventilation (adaptive support, controlled mechanical, intermittent mandatory, etc), continuous renal replacement therapy (CRRT) and other assistant treatments were selected to apply in specific cases. Short-acting insulin analogs were administrated subcutaneously to control hyperglycemia for partial patients.

Information regarding demographics, hospital course, and primary causes were documented. Nutrition parameters, consisting of the presence of EN and PN, duration of nutrition support, route of nutrient delivery, and elementary formulas of nutrition, were noted. The complications as well as the time of permanent abdominal closure were also noted.

(5 cases), pulmonary infection or respiratory failure (3 cases), septic shock (2 cases), and liver failure (1 case). Another 15 patients, who were otherwise manageable but chose to return home for terminal care, were confirmed to be dead. The mortality was markedly lower among patients fed within 14 days compared with those fed later (11.1% vs 47.8%, P < .001). The general demographics were reviewed among patients who received EN within 14 days compared with those who did not. There were no significant differences in age, body mass index (BMI), severity scores, primary disease, underlying disease, or characteristics of fistula across the two groups (Table 1). Trauma was the major primary insult to the abdomen, with 44 patients (53.6%, 41 males) involved. For all patients, the mean interval from primary disease developed to an open abdomen was 21.9 ± 22.4 days. The difference of the interval between the two groups was not significant (20.3 ± 15.6 vs 22.1 ± 20.3, P = .662).

Statistical Analysis

Nutrition Support

Descriptive statistics including mean ± SD or counts and percentages were used to describe the study population on all variables. Continuous variables were first checked for normal distribution using Shapiro-Wilk goodness-offit test and then compared by 2-tailed t test for normally distributed variables or a Wilcoxon rank-sum test for non-normally distributed variables. Univariable analysis was performed using χ2 or Fisher’s exact test for categorical data. All statistical analyses were performed by using the SPSS Software (version 16.0, SPSS Inc, Chicago, IL, USA). A P value < .05 was considered statistically significant.

Nutrition therapy, including EN, PN, or EN combined with PN, was provided to all patients as fundamental treatment. The duration of EN, and EN combined with PN, was similar in both groups, while the duration of PN was significantly prolonged among patients with delayed initiation of EN compared with those fed within 14 days (Table 2). However, the initiation time of PN was similar (1.0 ± 7.1 vs 1.6 ± 9.2 days, P = .642). PN was initiated in 20 patients prior to referral. The routes of enteral delivery for included oral feeding, nasogastric tube feeding, nasointestinal tube feeding, gastrostomy tube feeding, jejunostomy tube feeding, and orificium fistula feeding. At least one delivery method was performed for each patient in the study. In sum, 41 (50%) patients received SER to recover bowel continuity for continuous EN, 38 patients through nasogastric tube, and 29 patients through surgical jejunostomies. The initiation time of SER was earlier for patients fed within 14 days than for those fed later (P < .05, Table 1). Different kinds of EN products were used for all patients. Peptison (Nutricia, Shanghai, China) was provided to 85% of patients, with significant difference between the two groups (P = .01). The detailed selection of nutrients is shown in Table 3.

Nutrition Therapy Assessment

Results General Characteristics of Patients Ninety-two patients met the entry criteria during the interval of this study. Of this cohort, 10 patients died of irreversible septic shock within 4 days of admission and were not further considered. For all other patients, 82 (male-female ratio, 68:14) patients received open abdomen management and nutrition therapy with mean age of 44.4 ± 15.2 (range, 19–83) years. Enteral feedings were initiated within 14 days of hospital stay in 36 patients, with a mean initiation time of EN at 8.3 ± 3.4 days. The remaining 46 patients did not start any enteral feedings within the 14-day period, with a mean initiation of EN at 29.9 ± 20.9 days (P < .05). The overall mortality of all patients was 31.7% (26/82). Specifically, 11 patients died of intra-abdominal hemorrhage

Other Measures and Treatment Outcome CRRT was required in 16 patients for 10.1 ± 7.1 days, of whom 4 (25%) had been fed within 14 days. In addition, mechanical ventilation was performed in 47 patients for 25.1 ± 16.8 days, of whom 15 (31.9%) had been fed

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Nutrition Therapy for Intestinal Fistula After an Open Abdomen / Yuan et al   691

Table1.   Comparison of Groups Based on the Initiation Time of Enteral Nutrition Characteristic Age (y), mean ± SD BMI, mean ± SD Male gender, n (%) Severity score on admission   APACHE II  SOFA Mechanical ventilation, n (%) CRRT, n (%) Primary disease, n (%)  Trauma  Malignancyc  IBD  Miscellaneousd Cause of fistula, n (%)   Postoperative complication   Perforated viscus Fistula location, n (%)   Small bowel  Colon  Duodenum  Pancreas  Stomach   Multiple viscerae Fistula output(mL/day)   ≥500 (high)   200–500 (intermediate)