Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems

Purpose Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options. Methods The Working Group on Abdominal Problems (WGAP) of the European Society of Intensive Care Medicine (ESICM) developed the definitions for GI dysfunction in intensive care patients on the basis of the available evidence and current understanding of the pathophysiology. Results Definitions for acute gastrointestinal injury (AGI) with its four grades of severity, as well as for feeding intolerance syndrome and GI symptoms (e.g. vomiting, diarrhoea, paralysis, high gastric residual volumes) are proposed. AGI is a malfunctioning of the GI tract in intensive care patients due to their acute illness. AGI grade I = increased risk of developing GI dysfunction or failure (a self-limiting condition); AGI grade II = GI dysfunction (a condition that requires interventions); AGI grade III = GI failure (GI function cannot be restored with interventions); AGI grade IV = dramatically manifesting GI failure (a condition that is immediately life-threatening). Current evidence and expert opinions regarding treatment of acute GI dysfunction are provided. Conclusions State-of-the-art definitions for GI dysfunction with gradation as well as management recommendations are proposed on the basis of current medical evidence and expert opinion. The WGAP recommends using these definitions for clinical and research purposes. Electronic supplementary material The online version of this article (doi:10.1007/s00134-011-2459-y) contains supplementary material, which is available to authorized users.

Abstract Purpose: Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options. Methods: The Working Group on Abdominal Problems (WGAP) of the European Society of Intensive Care Medicine (ESICM) developed the definitions for GI dysfunction in intensive care patients on the basis of the available evidence and current understanding of the pathophysiology. Results: Definitions for acute gastrointestinal injury (AGI) with its four grades of severity, as well as for feeding intolerance syndrome and GI symptoms (e.g. vomiting, diarrhoea, paralysis, high gastric residual volumes) are proposed. AGI is a malfunctioning of the GI tract in intensive care patients due to their acute illness. AGI grade I = increased risk of developing GI dysfunction or failure (a self-limiting condition); AGI grade II = GI dysfunction (a condition that requires interventions); AGI grade III = GI failure (GI function cannot be restored with interventions); AGI grade IV = dramatically manifesting GI failure (a condition that is immediately life-threatening). Current evidence and expert opinions regarding treatment of acute GI dysfunction are provided. Conclusions: State-ofthe-art definitions for GI dysfunction with gradation as well as management recommendations are proposed on the basis of current medical evidence and expert opinion. The WGAP recommends using these definitions for clinical and research purposes.

Introduction
More than 10 years ago a round-table conference on gut dysfunction in critical illness concluded that intestinal function is an important determinant in the outcome of patients admitted to the intensive care unit (ICU), but that there is no objective and clinically relevant definition of gastrointestinal (GI) dysfunction in critical illness. In addition, it was stated that the definition developed in the future should grade the severity of dysfunction [1].
The problems in defining GI dysfunction start with defining GI function. Next to the digestive tract, the GI tract also carries out endocrine, immune and barrier functions. The clinical assessment of the impairment of these functions today is more intuitive than objective. Therefore, endocrine, immune and barrier dysfunctions will not be addressed in detail in the present paper.
Several studies have confirmed that GI symptoms are frequent in the ICU with up to 62% of patients exhibiting at least one GI symptom for at least 1 day [2][3][4]. There is also increasing evidence that development of GI problems is related to worse outcome in critically ill patients [2,[5][6][7].
Different definitions for separate GI symptoms have been used. The lack of markers for the measurement of GI function has suppressed studies in this field as well as the assessment of GI dysfunction as an organ failure. Although plasma citrulline and intestinal fatty acid binding protein have been proposed as possible markers for small bowel function [8], their clinical use in diagnosis and management of GI dysfunction is still unclear.
At least partly due to the lack of a formal definition and classification, treatment strategies for GI problems have been difficult to develop and are currently based on experience, rather than evidence.
There is increasing evidence that early protocolized and goal-oriented care can improve organ function and the patients' outcome during critical illness [9][10][11][12]. Improving the definition of GI dysfunction as a part of the multiple organ dysfunction syndrome (MODS) and its derived sequential organ failure assessment score (SOFA) [13] will establish the base for setting up the bundle of preventive and therapeutic measures and support the development of novel treatment strategies.
For these reasons, the Working Group on Abdominal Problems (WGAP) as part of the Perioperative Intensive Care (POIC) section of the European Society of Intensive Care Medicine (ESICM) proposes a set of definitions and grading system of GI dysfunction in critical illness that are applicable both for clinical and research purposes.

Methods
Several key elements were used as a starting point for defining acute GI organ failure. An organ failure was considered as a dichotomous event that is either present or absent, whereas organ dysfunction is a continuum of physiologic derangement [14]. The expression ''GI dysfunction'' is used to describe the large variety of GI symptoms (diarrhoea, vomiting) and diagnoses (gastroenteritis) outside of the ICU setting; therefore, the expression ''acute GI injury'' was introduced.
Current definitions and management recommendations (according to Table 1; [15]) were developed on the basis of the available evidence and current understanding of the pathophysiology. Definitions serve as expert opinion, with their reasoning given in each ''rationale'' subsection.
The working method is described in detail in the electronic supplementary file.

Results
The WGAP suggests using the following terminology and definitions:

Gastrointestinal function
The human GI tract has many functions including facilitating digestion to absorb nutrients and water, barrier control to modulate absorption of intraluminal microbes (and their products), endocrine and immune functions. Perfusion, secretion, motility and a coordinated gut-microbiome interaction are prerequisites for an adequate function [16]. It needs to be underlined that because we currently lack the tool or marker to measure GI function we cannot reliably decide about normal GI function in the acute setting. 2. Acute gastrointestinal injury (AGI) and its different grades Acute GI injury (AGI) is malfunctioning of the GI tract in critically ill patients due to their acute illness. According to severity the following grades of AGI can be distinguished:  [52][53][54].
Rationale There is no sufficient scientific evidence or physiological ground to define precise values for high gastric residuals [53,55]. Measurement of gastric residuals is neither standardized nor validated [56]. It has been suggested that gastric residual volume greater than 200 ml should prompt careful bedside evaluation, but automatic cessation of enteral nutrition solely on the basis on residual volumes of 200-500 ml should be avoided [53,56,57]. Despite the lack of scientific evidence, the members of the WGAP arbitrarily use total volumes of gastric residuals above 1,000 ml/ 24 h as a sign of abnormal gastric emptying, which requires specific attention. Management Intravenous administration of metoclopramide and/or erythromycin is recommended for management of high gastric residuals, whereas cisapride is no longer approved [58] (grade 1B). Routine use of motility agents is not recommended [58] (grade 1A). Acupuncture stimulation may facilitate gastric empting in neurosurgical ICU patients [59] (grade 2B). Use of opioids and deep sedation should be avoided/reduced if possible. Cessation of gastric feeding is suggested if residual volumes exceed 500 ml per single measurement [57]. Here, postpyloric feeding should be considered [58] (grade 2D). Routine application of postpyloric feeding is not advocated [58] (grade 2D). Postpyloric feeding may cause severe small bowel dilatation and perforation in rare cases. 5.3 Diarrhoea is defined as having three or more loose or liquid stools per day with a stool weight greater than 200-250 g/day (or greater then 250 ml/day) [60,61].
Rationale Normal bowel frequency ranges from three times a week to three times a day. Secretory, osmotic, motor and exudative diarrhoea may be distinguished [61], but in the ICU it is often better to distinguish between disease-, food/feeding-and drug-related diarrhoea [61,62]. Management Symptomatic therapy-replacement of fluids and electrolytes, haemodynamic stabilization and organ protection (e.g. correction of hypovolaemia to prevent impairment of renal function) forms the basic management [ Rationale Asymptomatic, endoscopically evident mucosal damage occurs in the majority of ICU patients [2]. Clinically evident GI bleeding reflecting considerable damage to GI mucosa may be seen in 5-25% of ICU patients [2]. Clinically important bleeding, defined as overt bleeding in association with haemodynamic compromise or the need for blood transfusions [70], occurs in 1.5-4% of mechanically ventilated patients [2,70,71]. Management In cases of clinically evident GI bleeding, the haemodynamic status dictates the approach. In cases of bleeding with haemodynamic instability endoscopy is the diagnostic tool of choice [72], but when bleeding is ongoing and massive, precluding adequate endoscopic assessment, angiography is appropriate (grade 2C  [84]. Management There are no special management suggestions for absent/abnormal bowel sounds. 5.7 Bowel dilatation is present if colonic diameter exceeds 6 cm (greater than 9 cm for caecum) or small bowel diameter exceeds 3 cm, diagnosed either on plain abdominal X-ray or CT scan [85,86].
Rationale Bowel dilatation is a common sign in obstruction at any level of the GI tract. Bowel dilatation may also appear without an obstruction; the terms toxic megacolon following colitis and acute colonic pseudo-obstruction or Ogilvie's syndrome, are used to describe acute severe colonic dilatation.  [92][93][94] (grade 1B), and may therefore prevent bowel dilatation. 6. Feeding protocols Decreased food intake and resulting malnutrition are independent risk factors for in-hospital mortality [95]. European Society for Parenteral and Enteral Nutrition (ESPEN) guidelines are available with recommendations for nutrition in intensive care [58]. Feeding protocols based on these guidelines should be implemented in every institution. Periods of interruption of enteral feeding due to various interventions in the hospital (surgery, diagnostic or therapeutic interventions, extubation) should be remembered and minimized [96,97]. Daily assessment of adequacy of enteral nutrition is required. 7. A schematic guideline for the management of patients with AGI is presented in Fig. 1.

Discussion
Terminology and definitions provided in the present paper were developed with the aim of providing clinical definitions which may be used in different ICUs and clinical situations.
Our working methods were similar to those commonly used for the consensus definitions and grading of evidence for the treatment recommendations. The main limitation of the current document is the lack of objective measures for GI function/dysfunction. As the evidence in this field is scarce, the definitions are largely based on expert opinion. Therefore, in case new established measures to assess GI function/dysfunction become available, proposed definitions need to be revised. The complete description of diagnostic procedures for conditions underlying AGI is not provided in the current manuscript, common clinical approach is presumed.
Our grading system is not based on a certain numeric variable and is not validated. With no doubt further research is needed to establish the measures of GI function that could be used in a reproducible manner for grading GI function. At present, the descriptions of the grades of AGI are complicated and the same grade of AGI may have different clinical expressions. It is likely that the score will in some extent be dependent on the treatment applied. In fact, other organ dysfunction scores (e.g. SOFA score) have also been developed first, and only validated afterwards. Moreover, the cardiovascular sub-score of SOFA [13], known to be the most performing among all the subscores, is defined as a mean arterial pressure and the usage/ dosage of vasoactive/inotropic agents, where the last part is clearly dependent on the local treatment traditions.
Despite the many well-known limitations which have been restraining the development in this area for so long, we need to move forward, and we suggest to start with the definitions proposed in this paper.

Summary
The terminology and definitions provided herein should allow better clinical communication as well as comparison between future studies. Defining the specific variables is the first step in a process towards better knowledge in this area. We propose a definition of acute gastrointestinal injury (AGI) with four grades of severity. AGI grade I stands for a self-limiting condition with increased risk of developing GI dysfunction or failure; AGI grade II (GI dysfunction) is a condition requiring interventions to restore GI function; AGI grade III (GI failure) is a condition when GI function cannot be restored with interventions; and AGI grade IV is dramatically manifesting GI failure, which is immediately life-threatening.
The WGAP of ESICM suggests using the proposed definitions until the results of a broader consensus are available. We encourage research to define explicit characteristics of GI function in critically ill patients.