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 Table of Contents  
Year : 2022  |  Volume : 1  |  Issue : 1  |  Page : 30-37

Intestinal rehabilitation in critical illness

1 LA Key Laboratory of Trauma and Surgical Infections, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
2 PLA Key Laboratory of Trauma and Surgical Infections, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China
3 PLA Key Laboratory of Trauma and Surgical Infections, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University; PLA Key Laboratory of Trauma and Surgical Infections, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China

Date of Submission28-Mar-2022
Date of Decision18-Apr-2022
Date of Acceptance19-Apr-2022
Date of Web Publication17-Jun-2022

Correspondence Address:
Jianan Ren
PLA Key Laboratory of Trauma and Surgical Infections, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002
Xiuwen Wu
PLA Key Laboratory of Trauma and Surgical Infections, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/wjsi.wjsi_7_22

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Intestinal rehabilitation is a treatment strategy to promote the resumption of enteral nutrition and transoral diet in the residual small intestine of patients with short bowel syndrome from the early stage, which mainly includes four phases: total parenteral nutrition, parenteral combined enteral nutrition, total enteral nutrition, and transoral diet. New meanings and indications have been continuously given in clinical practice over the years. It is currently being applied to treat gastrointestinal (GI) injuries in critical illnesses. This review discusses the current conditions of diagnosis of GI injury and intestinal rehabilitation treatment at home and abroad in critical illnesses.

Keywords: Critical illnesses, intestinal rehabilitation, nutrition

How to cite this article:
Li S, Liu P, Liu Y, Huang J, Wu X, Ren J. Intestinal rehabilitation in critical illness. World J Surg Infect 2022;1:30-7

How to cite this URL:
Li S, Liu P, Liu Y, Huang J, Wu X, Ren J. Intestinal rehabilitation in critical illness. World J Surg Infect [serial online] 2022 [cited 2022 Dec 9];1:30-7. Available from: https://www.worldsurginfect.com/text.asp?2022/1/1/30/347770

  Introduction Top

The gut is one of the most important and complex organs in the body, consisting of epithelium, immune system and microbiome, and plays an essential role in the maintenance of health and pathophysiology of critical illnesses.[1] The gut is considered the motor of multiple organ dysfunction in critical illness.[2],[3] Our early understanding of gastrointestinal (GI) dysfunction was not systematic and comprehensive because of the lack of a clear definition and objective criteria. Therefore, most of our diagnosis and treatment of patients' GI function is based on experience rather than following clear guideline evidence.[4] In addition, the lack of early-alert predictors with highly sensitive and specific is a crucial factor limiting clinical practice and researches.

In 2020, the Section of Metabolism, Endocrinology, and Nutrition of the European Society of Intensive Care Medicine (ESICM) jointly proposed a systematic review and research agenda for GI dysfunction in critically ill patients.[5] The agenda summarizes the five main aspects of monitoring, the relationship between GI dysfunction and prognosis, GI function and nutrition, the treatment of GI dysfunction, and the pathophysiological mechanism, focusing on key areas with insufficient clinical evidence. It provides a broader perspective and direction for future research.

Intestinal rehabilitation is a bundle of treatments that promotes the maximization of remaining intestinal function through pharmacological, surgical, and nutritional methods, allowing the patient to be completely or partially weaned from parenteral nutrition (PN).[6] In clinical practice, we found that the application of systematic intestinal rehabilitation therapy may be an effective means of treating acute GI injury (AGI) in critically ill patients and improving outcomes.

  The Development of Intestinal Rehabilitation Top

The concept of classical intestinal rehabilitation, which refers to the promotion of residual intestinal adaptation and intestinal rehabilitation after bowel resection through dietary modification, pharmacological treatment, and surgical procedures to meet the body's need for nutrient digestion and absorption, was first proposed and applied to the treatment of short bowel syndrome. In the middle of the last century, the most primitive intestinal rehabilitation therapy began to take shape. Meyer et al. reported the patient with short bowel syndrome who underwent complete resection of the small intestine below the middle colon artery opening, leaving only about 46 cm of jejunum.[7] During the 22 follow-up years, this patient can tolerate the adjusted diets, take a variety of trace elements daily, inject Vitamin B12 every week, defecate 2 to 3 times every day, and can maintain a normal social life.[8],[9] In 1966, Dowling et al. showed that the ability of the intestinal mucosa to absorb glucose can be compensatory increased after bowel resection.[10] This provides a theoretical basis for the later transition to enteral nutrition in patients who rely on PN in the early stages. In 1994, Lennard pointed out that “the future of research is the improvement of absorptive capacity through diet, drugs, and growth factors.”[11] In 1995, Byrne et al. proposed the promotion of intestinal adaptation as the target of pharmacological treatment, using growth hormone, glutamine, and modified diets to promote residual intestinal tube absorptive capacity.[12],[13],[14] This is the original definition of “intestinal rehabilitation.”

With the deepening of recognition in GI function and injury, intestinal rehabilitation has been given many new meanings in clinical practice. General intestinal rehabilitation refers to the promotion of maximum residual intestinal function through pharmacological, surgical and nutritional means, so that the patient can be completely or partially weaned off PN and gradually return to a transoral diet. General intestinal rehabilitation is applicable to GI injury caused by various diseases but is not limited to the treatment of short bowel syndrome. For AGI due to critical illness, intestinal rehabilitation is not only a treatment concept but also a practical treatment measure. In critical care, intestinal rehabilitation can be divided into four stages: total PN, parenteral combined with enteral nutrition, total enteral nutrition, and transoral diet.

  Gastrointestinal Injury and Treatment in Critical Illnesses Top

Intestinal rehabilitation is primarily aimed at maintaining the homeostasis of the GI environment, improving GI injury/failure, and shutting down the engine effect of the intestine. The purpose of this section is to describe the importance of using intestinal rehabilitation in critical illness, and the detailed mechanisms of injury and protection are not discussed here.

The concept of the gut being the motor of multiple organ dysfunction syndrome (MODS) and the undrained abscess of multiple organ failure (MOF) as described by Marshall and Meakins has altered considerably over recent years as our understanding of gut barrier dysfunction and bacterial translocation in humans has improved.[15] Specifically, the relationship in humans still remains circumstantial, and there is no level 1 evidence to directly connect the two. However, the understanding of the pathophysiological mechanisms of the intestine in critical illness is continuously updated.[3],[16],[17] To determine directly whether bacterial translocation occurs in humans, Deitch cultured mesenteric lymph nodes obtained from 42 patients undergoing dissection without clinical infection and found that simple intestinal obstruction of the colon or small intestine in the absence of necrotic bowel appeared to be associated with bacterial translocation.[18] The present studies show that some critical illnesses, such as trauma and infections, transfer to sepsis is mainly due to the translocation of intestinal bacteria. Intestinal barrier function is impaired, forming bacterial translocation, which is the most important biological event in sepsis.[2] In anatomical terms, the intestine in critical illness can be damaged sequentially from the mucosa and the muscularis to the plasma membrane. In functional terms, these morphological injuries are mostly accompanied by impairments in motor function, digestive and absorptive functions, and multiple barrier functions. These dysfunctions may lead to intestinal flora disorders, abdominal compartment syndrome, MODS, and MOF. Several clinical studies show that GI dysfunction is associated with poor prognosis in critical illness.[19]

The largest published study of factors independently associated with bacterial translocation and intestinal dysfunction found that 130 of 927 patients (14.0%) who underwent open surgery had bacterial translocation.[20] Postoperative sepsis was more common in patients with bacterial translocation (42.3% vs. 19.9%; P < 0.001). This study showed that only emergency surgery and preoperative PN use were associated with increased bacterial translocation in a multivariate analysis. The use of PN and gut dysfunction is obviously linked, and therefore, the finding of enhanced bacterial translocation was inevitable. Intestinal barrier dysfunction leads to distant organ injury, of which the lung is the most frequent and important. Dickson et al. detected abundant intestinal-specific bacteria (Mycobacterium spp.) in bronchoalveolar lavage fluid from patients who were diagnosed with ARDS, and confirmed a positive correlation with the degree of systemic inflammatory response.[21] In addition, intestinal tissue edema and mesenteric vasoconstriction due to intestinal inflammation can further amplify intestinal injury and even lead to nonocclusive mesenteric ischemia, which is a form of acute intestinal ischemia caused by spasm of the superior mesenteric artery. Nonocclusive mesenteric vascular ischemia is an end-stage manifestation of sepsis, congestive heart failure, cardiac arrhythmias, acute myocardial infarction and severe blood loss, with a high mortality rate.[22]

Current therapies for GI dysfunction rely mainly on the treatment of the primary disease and still lack specific treatment to maintain the mucosal integrity of the GI tract. It is more important to answer the question of how to control a series of immune disorder reactions triggered by the loss of mucosal integrity, such as systemic inflammatory response syndrome, and sepsis. Intestinal rehabilitation is a readily available and feasible treatment strategy. Early enteral nutrition significantly attenuates the inflammatory response in the intestine, restores intestinal villi morphology, and reduces intestinal epithelial cell apoptosis. This is an important theoretical basis for the use of enteral nutrition to significantly improve critical illness.[23] In addition, the reasonable administration of early PN is also necessary. Early PN may be protective against both muscle wasting and fat loss, while diaphragm function is a major determinant of the ability to successfully wean from invasive mechanical ventilation.[24] Mechanical ventilation harms the structure and function of the diaphragm. The muscle fibers were significantly atrophied after 18 h of mechanical ventilation.[25],[26] Early PN may result in some protection of diaphragm structure and function due to the overall protection of muscle mass, leading to improved respiratory mechanics during deconditioning and reduced ventilatory time.[27]

Besides the classical administration of parenteral and enteral nutrition, the management of intestinal microecology should also be included in the concept of intestinal rehabilitation. Research on the intestinal microenvironment has been booming in recent years.[1] The intestinal microbiota is important for a variety of intestinal functions, such as the fermentation and absorption of enteral nutrients, the establishment of the immune system, and the growth and integrity of the intestinal mucosa. In inflammatory bowel disease, the role of enteral nutrition in alleviating the inflammatory status of the intestine and maintaining intestinal remission has been widely demonstrated, although the exact mechanism is not clear.[28],[29] Imbalanced intestinal microbiota can increase susceptibility to sepsis by increasing pathogenic bacteria, initiating an inflammatory immune response, and decreasing beneficial flora products such as short-chain fatty acids.[30] In addition, the development of sepsis and antibiotic therapy targeting sepsis can further deteriorate the intestinal flora, leading to increased end-organ damage. Targeted flora therapies such as probiotics, synbiotic agents, and selective digestive purification may reduce the risk of sepsis. Specific characteristics of gut bacterial flora can predict intensive care unit (ICU) patients' progression.[31],[32],[33] The abundance of pathogenic species, such as Enterococci, was increased to varying degrees in deceased septic patients, suggesting that these species are potential biomarkers in ICU.[34] Liu et al. further demonstrated that ICU enterotypes are closely associated with clinical outcomes of patients.[35] During the development of sepsis or septic shock, ICU patients exhibit 2 dysbiosis patterns (ICU E1 group consists mainly of the genus Mycobacterium and a certain unclassified genus of Enterobacteriaceae; ICU E2 group consists mainly of Enterococcus spp.) and are not affected by age, sex, BMI, and external factors (infection site, antibiotic use, etc.); ICU E1 group is associated with the development of septic shock. Kentaro et al. found that prophylactic supplementation of synbiotics prevents sepsis patients from complicating enterocolitis and ventilator-associated pneumonia.[36] We believe that targeted interventions in the intestinal microenvironment are an important direction for future research in intestinal rehabilitation. In relation to the risk of developing a clinically important outcome, intestinal overgrowth is defined as ≥ 105 potential pathogens per milliliter of GI secretions, including “abnormal” aerobic Gram-negative bacilli, “normal” bacteria and yeasts, and is a key event prior to the development of primary and secondary endogenous infections.[37] Selective digestive tract decontamination (SDD) is antimicrobial prophylaxis designed to control overgrowth. SDD controls overgrowth by achieving high antimicrobial concentrations effective against “normal” and “abnormal” potential pathogens, rather than by selectively controlling overgrowth. A complete SDD regimen using parenteral and enteral antimicrobials can reduce lower respiratory infections by 72%, bloodstream infections by 37%, and mortality by 29%.

In addition, the acquired weakness in the ICU characterized by malnutrition due to the metabolic disorders of the body caused by the primary disease and the long-term lack of a regular transoral diet are important factors affecting the regression of acute critical illness.[38] Girard et al. summarized these patients with the concept of chronic critical illness.[72] In recent years, concepts such as “persistent inflammation, immunosuppression, and catabolism syndrome”[39] and “persistent critical illness”[40],[41] have been proposed, although with its focus, to describe a category of patients who are too weak to leave the ICU.[42] The original aim of intestinal rehabilitation is to increase the absorptive capacity of the remaining intestine through a series of planned treatments, which is particularly evident in the treatment of short-bowel syndrome.[43] Improving intestinal absorption dysfunction can increase the effectiveness of nutritional therapy and thus prevent chronic critical illness.[44] In addition, by adding additional nutritional factors, drugs and vitamins, maintaining intestinal barrier function and preventing intestinal bacterial translocation can prevent multi-organ dysfunction and reduce the incidence of mortality and chronic critical illness.[45] The administration of a systemic treatment strategy based on intestinal rehabilitation will be another important future direction for research in critical care medicine.

  Monitoring of Gastrointestinal Injury Top

Symptoms of GI injury are nonspecific. Currently, techniques to monitor GI dysfunction in critically ill patients are limited.[46] The evaluation of GI injury is also not included in mainstream illness severity scores, such as sequential organ failure assessment score,[47] acute physiology and chronic health evaluation II (APACHE II) score.[48] This may be because for the group that formulated the critical care scoring system, there was no acceptable metric for evaluating the degree of intestinal damage. This has led critical care investigators to ignore the extent of intestinal injury in patients when using these scores to evaluate baseline data of patients.[49] However, the degree of intestinal injury is essential in the evaluation of the critically ill patients' underlying condition, the adjustment of medical decisions, and the clinical prognosis of the regression.[50] Since there is no consensus on the best way to measure the severity of intestinal injury/failure, how to determine the time to start intestinal rehabilitation therapy and to detect the effects of rehabilitation are still important issues that have yet to be studied in the clinic.

Varsha et al. highlighted the limited applicability of existing scores to critically ill patients by comparing 14 GI dysfunction scoring tools that have been reported in the literature.[19] On the one hand, it provides a rather objective evaluation of the existing scores, and on the other hand, it provides a reference for the establishment of a more clinically useful GI function scoring system. The method widely used in clinical practice for measuring gastric residual volume has significant limitations in the assessment of total GI function. Increased gastric residual volume is an important manifestation of feeding intolerance during enteral nutrition, but it only refers to the poor dynamic function of the GI tract and lacks evaluation of its absorption and barrier function.[51]

The Working Group on Abdominal Problems as part of the perioperative intensive care section of the ESICM proposes a set of definitions and grading systems of GI dysfunction in critical illness that is applicable both for clinical and research purposes in 2012.[52] It clarifies the definition of four severity levels of AGI. Provide terms and definitions for better clinical communication and comparison between future studies. AGI is the malfunctioning of the GI tract in critically ill patients due to their acute illness, which can be divided into primary and secondary. Primary AGI is caused by a primary disease or direct injury to the GI tract. It is commonly reported in the early stages of GI injuries, such as peritonitis, abdominal surgery, and abdominal trauma. Secondary AGI is caused by severe illness or injury to tissues and organs other than the GI tract, no primary disease of the GI tract at the beginning of the disease, and AGI is the result of a second strike, such as AGI that occurs after pneumonia, heart disease, nonabdominal surgery or trauma, or cardiopulmonary resuscitation [Table 1].
Table 1: Acute gastrointestinal injury four grades

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Correcting existing malnutrition, which preparing for surgery and recovery, is another major aim of administering intestinal rehabilitation. However, in critically ill patients, weight or BMI does not accurately reflect their nutritional status because of the influence of fluid resuscitation, abnormal metabolism, and other pathological factors. The European Society for Clinical Nutrition and Metabolism guideline recommended a general clinical assessment, including weight change, physical examination, general assessment of body composition, and muscle mass and strength, to assess malnutrition in ICU.[53] Clinicians rely on clinical experience heavily in assessing nutritional status and making medical decisions. The American Society for Parenteral and Enteral Nutrition guideline recommended nutritional risk determination using the nutrition risk screening 2002 (NRS2002) and the nutrition risk in critically ill (NUTRIC) score to determine which patients could benefit from nutritional support.[54] However, the nutritional risk scale is a risk assessment of critically ill patients at the time of admission and does not reflect the effect after treatment. Haines et al. used the urea/creatinine ratio and changes in the cross-sectional area of the psoas muscle at the level of the L3 and L4 vertebrae in their study to measure muscle catabolism in critically ill patients.[55] Compared to general clinical assessments and nutritional risk scales, which are subjective, this is a more objective evaluation method that has been reported in the literature. There is wide variation in how nutritional status is evaluated, but there is no doubt that all ICU inpatients need to be screened for nutrition within 48 h of admission. Any critically ill patient who stays in the ICU for more than 48 h should be considered at risk for malnutrition, while intestinal rehabilitation should be started as early as possible.[53]

  Management of Intestinal Rehabilitation Top

The old theory of “gastrointestinal rest” has been discouraged in the last 30 years by the popularity of the theory of gut bacterial translocation.[56] Prolonged “gastrointestinal rest” leads to a lack of intraluminal nutrition of the intestinal mucosa, which in turn leads to intestinal barrier dysfunction and liver function injury.[57],[58] Critically ill patients receiving early total PN had a significantly impaired intestinal barrier, as evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal tight junction protein expression.[23] However, when GI dysfunction occurred in patients complicated with inflammatory edema of the intestinal wall, extensive adhesions in the small intestine, or persistent intestinal paralysis, it was wise to carry out the “gastrointestinal rest” by stopping enteral nutrition. Forced administration of enteral nutrition, especially total enteral nutrition, may increase the burden on the stomach and intestines, aggravate the AGI, and cause complications such as intestinal perforation and intestinal necrosis. In this case, total PN can be used to supplement the nutritional substrate, combined with growth inhibitors and GI de-pressure. This not only helps to reduce the edema of the intestinal wall, reduce the secretion of intestinal fluid, but also helps to reduce intestinal contents and intra-abdominal pressure, thus achieving the purpose of giving “gastrointestinal temporary rest” and eventually restoring the function of the GI tract. Therefore, early PN should not be completely abandoned because of the risk of increasing the incidence of infectious complications.[59] Doig et al. demonstrated in a randomized controlled clinical study that early PN in critically ill patients with relative contraindications to short-term enteral nutrition was not significantly harmful to patients' outcome.[60] In contrast, the duration of invasive mechanical ventilation can be reduced by early PN. The administration of PN within 24 h of ICU admission did not result in a significant difference in 60-day mortality or the rate of ICU-acquired infections. But interestingly, this did not significantly reduce the length of stay in ICU or hospital. A randomized, controlled, multicenter, open-label, parallel-group study showed that for patients in severe shock, the incidence of vomiting, diarrhea, intestinal ischemia, and acute pseudo-intestinal obstruction was higher in the early enteral nutrition group than in the early PN group.[61]

Enteral nutrition is a trump card for intestinal rehabilitation, but feeding intolerance is its main complication. Enteral nutrition should be tried repeatedly in patients with AGI. Early enteral nutrition, i.e., initiated within 48 h of ICU admission, is included in the critical care nutrition guidelines.[53],[54] Enteral nutrition is not always applied in full volume. By providing 1/4 of the body's total energy needs through the intestine, the pharmacological effect of enteral nutrition to improve intestinal barrier function can be achieved.[23] However, the administration of early enteral nutrition is not ideal. A multicenter clinical study covering 118 ICUs in 116 hospitals showed that only 32.7% of critically ill patients received enteral nutrition within 48 h of ICU admission.[62] Multivariate analysis identified AGI as a major obstacle to the initiation of enteral nutrition. Interestingly, Jin et al. showed that the rate of secondary infection was significantly lower in the early enteral nutrition group than in the late enteral nutrition group.[63] Regression analysis showed early enteral nutrition as a protective factor for secondary infection. The early enteral nutrition group had better improvement in AGI grading and serum albumin levels, and the percentage of enteral nutrition-related bloating was significantly reduced. The above evidence suggests that AGI is not a contraindication to initiating enteral nutrition and is not specified as such in the guidelines. In addition to the timing of enteral nutrition administration, the choice of enteral nutrition energy density is also a hotspot issue. For critically ill patients, the guidelines recommend matching energy intake with energy expenditure to prevent cumulative energy deficits, which are associated with poor outcomes.[53],[54] A single-center study showed that the combination of high-calorie delivery and organ failure increases mortality in patients with acute respiratory distress syndrome.[64] Compared to patients with low organ failure and low-calorie delivery, patients with high-caloric delivery and low organ failure, low-calorie delivery and high organ failure, and a combination of high organ failure and high-calorie delivery have a progressively higher mortality rate. The degree of organ dysfunction in critically ill patients has important implications for energy requirements and prognosis. A multicenter, double-blind, randomized controlled study showed that high-energy-density compared to regular energy density (1.5 Kcal/ml vs. 1.0 Kcal/ml) did not affect survival time, days rely on organ support, survival and discharge from the ICU and hospital or organ support, or the incidence of infectious complications or adverse events.[65] However, this study was controversial in terms of energy density infusion criteria and grouping.[66],[67] After resuming total enteral nutrition for some time, do not rush to resume a transoral diet, especially the total transoral diet. The GI tract can tolerate 24-h continuous tube feeding of enteral nutrition solution, but it may not be able to tolerate the one-time “meal” transoral diet. The enteral nutrition was gradually reduced, while the transoral diet was gradually increased, and the transoral diet was steadily restored.

Even if the oral diet is allowed, it is not a random diet for patients but a diet with a full range of nutrients and enough energy and protein as directed by a nutritionist. Patients are prevented from having the partial diet leading to poor nutrient intake or aggravating AGI due to gluttony. As our understanding of GI injury and failure continues to advance, the connotation of intestinal rehabilitation should also be enriched. In recent years, the concept of precision nutrition has emerged.[68] Precision nutrition is derived from the theory of nutritional genome, which refers to the identification of individual differences in nutrient absorption ability based on genomics and the selection of nutrients suitable for each individual based on the differences, to achieve nutritional balance.[69],[70] Precision nutrition provides multidimensional and dynamic nutritional recommendations, i.e., precise nutritional interventions for the right person, at the right time, to achieve health.[71] We believe the organic integration of precision nutrition and intestinal rehabilitation will lead to more specific treatment strategies and better therapeutic results.

  Conclusion Top

Under the multidisciplinary medical model, the connotation of intestinal rehabilitation has not only been updated but also no longer limited to the treatment of short bowel syndrome. Intestinal rehabilitation in a broad sense can be applied to various critically ill patients with GI function injury. Patients in the ICU have the characteristics of high heterogeneity and fluctuating conditions. For the acute critical illness period, postresuscitation, recovery period, and chronic critical illness period, different intestinal rehabilitation strategies should be considered individually. However, the lack of tools for early and accurate determination of GI injury in critically ill patients is a problem that needs to be solved urgently. This determines the time for intestinal rehabilitation to start, adjust, and stop. Combining the existing AGI grades, starting intestinal rehabilitation for the corresponding patients as soon as possible, focusing on the sequential use of parenteral and enteral nutrition, and scientific and reasonable supplementation of nutritional factors are essential to improve the prognosis of critically ill patients.

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