Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients.

We conducted a prospective, observational cohort study designed to compare intestinal permeability (IP) and development of multiple organ dysfunction syndrome (MODS) in a subset of critically ill patients in an intensive care unit (ICU). All patients with an expected ICU stay of 72 h or more were entered into the study, and IP was determined on a daily basis whenever possible from the urinary fractional excretion of orally administered lactulose and mannitol (LMR). Forty-seven consecutive patients were studied, and 28 developed MODS either at the time of admission or during their ICU course. These patients, as a group, had significantly worse IP at admission than did a non-MODS cohort (LnLMR: -2.10 +/- 1.10 versus -3.26 +/- 0.83). Those patients who developed MODS following admission also had a significantly greater admission IP than did the non-MODS group (-2.51 +/- 0.85). Differences in IP between cohorts could not be explained by differences in the incidence of systemic inflammatory response syndrome (SIRS)/sepsis or shock. With multivariate regression analysis, the only parameter present on admission that was predictive of subsequent MODS was IP. Differences in IP and the severity of organ dysfunction were also present (MODS severity mild: -3.01 +/- 0.72; moderate: -1.97 +/- 0.69; and severe: -1.12 +/- 0.96). Patients who developed MODS had a persistently abnormal IP during their ICU stay, and a significantly delayed improvement in their IP compared with the non-MODS cohort. We conclude that the development of MODS is associated with an abnormal and severe derangement of IP that is detectable prior to the onset of the syndrome. This observation lends credence to the premise that gastrointestinal (GI) dysfunction may be causally associated with the development of MODS in the critically ill patient.

[1]  C. Natanson,et al.  Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. , 1997, Critical care medicine.

[2]  D. Treacher,et al.  Gastrointestinal permeability and absorptive capacity in sepsis. , 1996, Critical care medicine.

[3]  J. Bion,et al.  Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. , 1996, JAMA.

[4]  C. Sprung,et al.  Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. , 1995, Critical care medicine.

[5]  A. Macpherson,et al.  Intestinal permeability: an overview. , 1995, Gastroenterology.

[6]  T. Peters,et al.  Comparison of four markers of intestinal permeability in control subjects and patients with coeliac disease. , 1994, Scandinavian journal of gastroenterology.

[7]  A. Macpherson,et al.  The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass. , 1994, Gastroenterology.

[8]  F. Cerra,et al.  Multiple organ failure syndrome in the 1990s. Systemic inflammatory response and organ dysfunction. , 1994, JAMA.

[9]  S. H. Sorensen,et al.  A novel HPLC method for the simultaneous quantification of monosaccharides and disaccharides used in tests of intestinal function and permeability. , 1993, Clinica chimica acta; international journal of clinical chemistry.

[10]  G. V. Poole,et al.  The role of infection in outcome of Multiple Organ Failure. , 1993, The American surgeon.

[11]  G. May,et al.  Is small intestinal permeability really increased in relatives of patients with Crohn's disease? , 1993, Gastroenterology.

[12]  A. Khaghani,et al.  Cardiopulmonary bypass impairs small intestinal transport and increases gut permeability. , 1993, The Annals of thoracic surgery.

[13]  J. Horton,et al.  Oxygen radicals, lipid peroxidation, and permeability changes after intestinal ischemia and reperfusion. , 1993, Journal of applied physiology.

[14]  M. Pasquale,et al.  Secondary organ dysfunction. From clinical perspectives to molecular mediators. , 1993, Critical care clinics.

[15]  R. Roumen,et al.  Intestinal permeability after severe trauma and hemorrhagic shock is increased without relation to septic complications. , 1993, Archives of surgery.

[16]  D. Rattner,et al.  Gut macromolecular permeability in pancreatitis correlates with severity of disease in rats. , 1993, Gastroenterology.

[17]  A. Pearson,et al.  Simultaneous quantification of mannitol, 3-O-methyl glucose, and lactulose in urine by HPLC with pulsed electrochemical detection, for use in studies of intestinal permeability. , 1993, Clinical chemistry.

[18]  U. Haglund Systemic mediators released from the gut in critical illness , 1993, Critical care medicine.

[19]  C. Ryan,et al.  Increased gut permeability early after burns correlates with the extent of burn injury , 1992, Critical care medicine.

[20]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[21]  S. Travis,et al.  Intestinal permeability: functional assessment and significance. , 1992, Clinical science.

[22]  F. Cerra,et al.  Multiple organ failure syndrome. , 1990, Disease-a-month : DM.

[23]  R. V. van Elburg,et al.  Intestinal permeability in pediatric gastroenterology. , 1992, Scandinavian journal of gastroenterology. Supplement.

[24]  R. Berg,et al.  Endotoxin‐induced bacterial translocation and mucosal permeability: Role of xanthine oxidase, complement activation, and macrophage products , 1991, Critical care medicine.

[25]  M. Fink,et al.  Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor. , 1991, Archives of surgery.

[26]  R. Berg,et al.  Studies of the route, magnitude, and time course of bacterial translocation in a model of systemic inflammation. , 1991, Archives of surgery.

[27]  J. Madara,et al.  Warner-Lambert/Parke-Davis Award lecture. Pathobiology of the intestinal epithelial barrier. , 1990, The American journal of pathology.

[28]  R. Berg,et al.  Hemorrhagic shock-induced bacterial translocation: the role of neutrophils and hydroxyl radicals. , 1990, The Journal of trauma.

[29]  R. Berg,et al.  Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats. , 1990, Critical care medicine.

[30]  E. Deitch Intestinal permeability is increased in burn patients shortly after injury , 1990, Surgery.

[31]  J. Macho,et al.  Rational approach to the management of multiple systems organ failure. , 1989, Critical care clinics.

[32]  W. Knaus,et al.  Multiple systems organ failure: epidemiology and prognosis. , 1989, Critical care clinics.

[33]  T. Ziegler,et al.  Increased intestinal permeability associated with infection in burn patients. , 1988, Archives of surgery.

[34]  Fiddian-Green Rg Splanchnic ischaemia and multiple organ failure in the critically ill. , 1988 .

[35]  R. Berg,et al.  Endotoxin promotes the translocation of bacteria from the gut. , 1987, Archives of surgery.

[36]  R. Sjödahl,et al.  An experimental model for studying reversible intestinal ischemia. , 1987, Acta chirurgica Scandinavica.

[37]  J. Marshall,et al.  Multiple-organ-failure syndrome. , 1986, Archives of surgery.

[38]  W. Knaus,et al.  APACHE II: a severity of disease classification system. , 1985 .

[39]  A. So,et al.  INTESTINAL PERMEABILITY AND INFLAMMATION IN RHEUMATOID ARTHRITIS: EFFECTS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS , 1984, The Lancet.

[40]  D. Cullen,et al.  Therapeutic Intervention Scoring System: Update 1983 , 1983, Critical care medicine.

[41]  S. Ukabam,et al.  Abnormal small intestinal permeability to sugars in patients with Crohn's disease of the terminal ileum and colon. , 1983, Digestion.