Mark T. DeMeo

North American Summit on Aspiration in the Critically Ill Patient: Consensus Statement

Aspiration is the leading cause of pneumonia in the intensive care unit and the most serious complication of enteral tube feeding (ETF). Although aspiration is common, the clinical consequences are variable because of differences in nature of the aspirated material and individual host responses. A number of defense mechanisms normally present in the upper aerodigestive system that protect against aspiration become compromised by clinical events that occur frequently in the critical care setting, subjecting the patient to increased risk. The true incidence of aspiration has been difficult to determine in the past because of vague definitions, poor assessment monitors, and varying levels of clinical recognition. Standardization of terminology is an important step in helping to define the problem, design appropriate research studies, and develop strategies to reduce risk. Traditional clinical monitors of glucose oxidase strips and blue food coloring (BFC) should no longer be used. A modified approach to use of gastric residual volumes and identification of clinical factors that predispose to aspiration allow for risk stratification and an algorhythm approach to the management of the critically ill patient on ETF. Although the patient with confirmed aspiration should be monitored for clinical consequences and receive supportive pulmonary care, ETF may be continued when accompanied by appropriate steps to reduce risk of further aspiration. Management strategies for treating aspiration pneumonia are based on degree of diagnostic certainty, time of onset, and host factors.

Intestinal permeation and gastrointestinal disease.

The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier; these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohns disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.

Acute pancreatitis in children

OBJECTIVES:Currently, there is no scoring system for predicting severity in acute pancreatitis in children. Our intent was to evaluate the performance of existing scoring systems in children, to develop a system for children, and to examine the etiology of acute pancreatitis in children.METHODS:A chart review of children with acute pancreatitis was conducted at six centers, three serving as criterion centers and three as validation centers. Ranson and Glasgow scores were calculated for each admission. Additional clinical data were collected, and parameters correlating with severity were incorporated into a new scoring system. Performance characteristics were calculated for each system.RESULTS:A total of 301 admissions were reviewed, 202 in the criterion group and 99 in the validation group. Eight parameters were included in a new scoring system for children. The parameters were as follows: age (<7 yr), weight (<23 kg), admission WBC (>18,500), admission LDH (>2,000), 48-h trough Ca2+ (<8.3 mg/dl), 48-h trough albumin (<2.6 g/dl), 48-h fluid sequestration (>75 ml/kg/48 h), and 48-h rise in BUN (>5 mg/dl). When the cut-off for predicting a severe outcome was set at 3 criteria, the new system had better sensitivity versus Ranson and Glasgow scores (70% vs 30% and 35%, respectively) and a better negative predictive value (91% vs 85% and 85%). The specificity (79% vs 94% and 94%) and positive predictive value (45% vs 57% and 61%) fell slightly.CONCLUSION:The new scoring system performs better in this group than do existing systems.

Mastocytic Enterocolitis: Increased Mucosal Mast Cells in Chronic Intractable Diarrhea

CONTEXT In some adult patients with chronic intractable diarrhea, the diagnosis remains elusive even after detailed evaluations, and colonic or duodenal biopsy specimens may appear unremarkable on routine hematoxylin-eosin staining. OBJECTIVES To assess the concentration of mast cells in colonic or duodenal biopsy specimens by immunohistochemical analysis for mast cell tryptase from patients with chronic intractable diarrhea and to evaluate their response to drugs affecting mast cell function. DESIGN Mast cells per high-power field were assessed in biopsy specimens from 47 patients with chronic intractable diarrhea, from 50 control subjects, and from 63 patients with other specific diseases that cause chronic diarrhea (inflammatory bowel disease, celiac disease, collagenous colitis, and lymphocytic colitis). Patients with chronic intractable diarrhea who had more than 20 mast cells per high-power field were administered drugs affecting mast cell mediator function and release. RESULTS The mean +/- SD concentration of mast cells in the 50 control subjects was 13.3 +/- 3.5 cells per high-power field; hence, patients with more than 20 mast cells per high-power field were considered to have increased mast cells. Thirty-three (70%) of 47 patients with chronic intractable diarrhea had increased mast cells, and symptoms were controlled by drug therapy in 22 (67%) of the 33 patients. No patient had systemic or cutaneous mastocytosis. No increase in mast cells was seen in patients with other common causes of chronic diarrhea. CONCLUSIONS In chronic intractable diarrhea, colonic or duodenal biopsy specimens may appear unremarkable on routine hematoxylin-eosin staining, but increased mast cells may be demonstrated by immunohistochemistry for mast cell tryptase, with the novel term mastocytic enterocolitis describing this condition. Similar increases in mast cells are not apparent in control populations or in patients with other specific diseases that cause chronic diarrhea. The cause of the increased mast cells remains to be elucidated.

Atopic irritable bowel syndrome: a novel subgroup of irritable bowel syndrome with allergic manifestations

BACKGROUND Mast cells have a primary role in atopy. Mast cells may play a unique role in a subgroup of patients with irritable bowel syndrome (IBS). This observation suggests a link between atopic disorders and IBS. OBJECTIVE To determine whether there is an association between atopic disorders and IBS. METHODS We undertook a prospective study using structured questionnaires. We administered questionnaires to 125 consecutive patients seen in the following clinics from July 1 through October 31, 2001: allergy/immunology (AI) (n = 39), gastroenterology (n = 36), and general medicine (n = 50). The survey included questions detailing gastrointestinal and allergic symptoms. Diagnosis of IBS was based on Rome II criteria. Diagnosis of atopy was based on clinical parameters. RESULTS The AI clinic reported a significantly (P = .015) higher rate of IBS than the general medicine clinic. The IBS incidence reported in the AI clinic was similar to that reported in the gastroenterology clinic. The likelihood of IBS was significantly higher in patients with seasonal allergic rhinitis (2.67 times; 95% confidence interval [CI], 1.10-6.49; P = .03), patients with allergic eczema (3.85 times; 95% CI, 1.72-8.60; P = .001), and patients with depression (2.56 times; 95% CI, 1.05-6.14; P = .04). Patients reporting atopic symptoms (seasonal allergic rhinitis, allergic eczema, and asthma) were 3.20 times (95% CI, 1.20-8.50) (P = .02) more likely to fulfill the criteria for IBS. CONCLUSIONS Adults with atopic symptoms report a high incidence of IBS, suggesting a link between atopy and IBS. We proposed a subgroup of patients with IBS (atopic IBS) who have typical IBS symptoms in association with atopic manifestations. Identifying atopic vs nonatopic IBS may help in identifyingthe underlying pathophysiologic mechanisms and therapeutic options.

Beneficial effect of a bile acid resin binder on enteral feeding induced diarrhea

Objectives:Diarrhea is a complication of enteral feeding, occurring in up to 68% of critically ill patients. We hypothesized that prolonged fasting results in abnormal bile acid homeostasis. Subsequent enteral feeding then causes a relative luminal excess of bile acids, which leads to choleretic diarrhea. Hence, diarrhea induced by enteral feeding should improve with the use of a bile acid binding agent, such as Colestid Granules.Methods:We evaluated the effect of Colestid on enteral feeding-induced diarrhea in a double-blind placebo-controlled study. Nineteen patients who were nil per os (NPO) for 5 days before initiation of enteral feeding were enrolled in the study and treatment continued for 7 days. The severity and frequency of diarrhea were quantified. Fecal bile acids were measured enzymatically. Stool nutrient loss was measured by fat extraction, microkjeldahl determination of nitrogen, and bomb calorimetry of dried fecal specimens.Results:Enteral feeding resulted in a high frequency of diarrhea (95%) at some time during the observation period. The majority of episodes of diarrhea in both groups were of low volume. Colestid significantly decreased the prevalence and severity of diarrhea. Colestid had no significant effect on fecal calorie or nutrient losses. The average bile acid concentration in the stool increased significantly after enteral feeding.Conclusion:Enteral feeding-induced diarrhea is, at least in part, due to malabsorption of bile acids. The bile acid resin binding agent Colestid improves diarrhea induced by enteral feeding.

Safety and Efficacy of Glucomannan for Weight Loss in Overweight and Moderately Obese Adults

Background. Few safe and effective dietary supplements are available to promote weight loss. We evaluated the safety and efficacy of glucomannan, a water-soluble fiber supplement, for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets. Methods. Participants were randomly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL (8 ounces) of water one hour before breakfast, lunch, and dinner for 8 weeks. The primary efficacy outcome was change in body weight after 8 weeks. Other efficacy outcomes were changes in body composition, hunger/fullness, and lipid and glucose concentrations. Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels. Results. A total of 53 participants (18–65 years of age; BMI 25–35 kg/m2) were enrolled and randomized. The two groups did not differ with respect to baseline characteristics and compliance with the study supplement. At 8 weeks, there was no significant difference between the glucomannan and placebo groups in amount of weight loss (−.40 ± .06 and −.43 ± .07, resp.) or other efficacy outcomes or in any of the safety outcomes. Conclusions. Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition, hunger/fullness, or lipid and glucose parameters. This trial is registered with NCT00613600.

The Effects of Bowel Preparation on Microbiota-Related Metrics Differ in Health and in Inflammatory Bowel Disease and for the Mucosal and Luminal Microbiota Compartments.

OBJECTIVES:Bowel preparations (BPs) taken before colonoscopy may introduce a confounding effect on the results of gastrointestinal microbiota studies. This study aimed to determine the effect of bowel preparation on the mucosa-associated and luminal colonic microbiota in healthy subjects (HC) and inflammatory bowel disease (IBD) patients.METHODS:Biopsy samples (n=36) and fecal samples (n=30) were collected from 10 HC and 8 IBD subjects pre- and post-BP. 16S rRNA gene was pyrosequenced using 454 Titanium protocols. We compared the differences between the pre- and post-BP samples (i.e., comparisons-across-bowel-prep); we examined the effect of BP on the expected separation of the mucosal vs. the luminal compartments (i.e., comparisons-across-compartments). Last, we compared the baseline differences between the HC vs. IBD groups (a secondary analysis), and examined whether the differences between the HC vs. IBD changed after BP.RESULTS:In comparisons-across-bowel-prep, the Shannon’s index (SI) decreased only in the biopsy samples of IBD subjects post-BP (P=0.025) and phylogenetic diversity-whole tree (PD-WT) metric decreased in biopsy samples of HC subjects post-BP (P=0.021). In secondary comparisons, the subtle differences between the fecal samples of the HC vs. IBD groups, in terms of evenness and the SI, were not apparent post-BP. In terms of β-diversity, in comparisons-across-bowel-prep, the proportion of shared operational taxonomic units (OTUs) in pre- and post-BP samples was low (~30%) and unweighted Unifrac distances between pre- and post-BP specimens ranged from 0.52 to 0.66. HC biopsies were affected more than IBD biopsies with BP (P=0.004). In comparisons-across-compartments, the proportion of shared OTUs between biopsy and fecal samples increased and Unifrac distances decreased post-BP in IBD subjects, reducing the differences between the mucosal and luminal compartments of the gut microbiota. Interindividual differences in Unifrac distances were preserved even with BP effects, although the effects were greater on weighted Unifrac distances. Bacteroidetes and its subtypes increased post-BP in both the luminal and mucosal compartments.CONCLUSIONS:Bowel preparations affect the composition and diversity of the fecal and luminal microbiota in the short term, introducing potential bias into experiments examining the gut microbiota. The magnitude of the effect of BP is not greater than that of interindividual variation. Both the luminal and mucosal compartments of the gut microbiota get affected, and samples from controls and IBD subjects may get affected differently. Studies of the colonic microbiota should take into account the direction and the magnitude of the change introduced by BP during the design stage of the experiments, and consider sample sizes so that potential bias is minimized.

Physiology of the aerodigestive system and aberrations in that system resulting in aspiration.

BACKGROUND Aspiration pneumonia remains a significant and often devastating problem in critically ill patients. It is unclear whether aspiration pneumonia occurs because of problems in the handling of oropharyngeal secretions or if the reflux of gastric contents is the major etiological factor. Additionally, the obvious breakdown of upper aerodigestive protective mechanisms in the critically ill patient population is largely unstudied. Finally, the impact and contribution of tubes, both endotracheal and nasoenteral, on aspiration pneumonia is unclear. METHODS A Medline literature search on scientific and review articles concerning the normal physiology of the aerodigestive tract and factors that compromised normal physiology was undertaken. Readings were supplemented by expert outside opinion from researchers in these fields and from the combined expertise from a multidisciplinary panel of experts assembled at a recent summit on aspiration pneumonia. RESULTS Changes in the normal physiology of the aerodigestive tract are vast and varied and dependent on the response to injury, iatrogenic interventions, and the use of nasoenteral and endotracheal tubes. The effects on gastric and esophageal motility are likely dynamic and represent an ongoing but changing risk of reflux for the patient. Nasoenteral and endotracheal tubes likely compromise upper aerodigestive protective mechanisms. CONCLUSIONS More research is needed on the functioning of the aerodigestive protective mechanisms in critically ill patients. Understanding of the dynamic changes in gastrointestinal motility will also be an important factor to decrease the incidence of aspiration pneumonia in this patient population.

Erythromycin in chronic intestinal pseudo-obstruction.

To the Editor: Chronic intestinal pseudo-obstruction is an uncommon syndrome of impaired gut motility (1). Characteristic symptoms are suggestive of intestinal obstruction, but without evidence of a fixed mechanical lesion. Various pharmacological agents have been used in the treatment of these patients, usually with disappointing results. Erythromycin, a macrolide antibiotic, has been shown to be a prokinetic intestinal motility agent in both man and animals (2,3). To our knowledge, it has not been previously used in the treatment of patients with this disorder.