Intestinal Injury in Ugandan Children Hospitalized With Malaria
Michelle NgaiMichael HawkesClara EriceAndrea M. WeckmanJulie WrightVeselina StefanovaRobert O. OpokaSophie NamasopoAndrea L. ConroyKevin C. Kain
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Abstract Background Severe malaria is associated with multiple organ dysfunction syndrome (MODS), which may involve the gastrointestinal tract. Methods In a prospective cohort study in Uganda, we measured markers of intestinal injury (intestinal fatty-acid binding protein [I-FABP] and zonula occludens-1 [ZO-1]) and microbial translocation (lipopolysaccharide binding protein [LBP] and soluble complement of differentiation 14 [sCD14]) among children admitted with malaria. We examined their association with biomarkers of inflammation, endothelial activation, clinical signs of hypoperfusion, organ injury, and mortality. Results We enrolled 523 children (median age 1.5 years, 46% female, 7.5% mortality). Intestinal FABP was above the normal range (≥400 pg/mL) in 415 of 523 patients (79%). Intestinal FABP correlated with ZO-1 (ρ = 0.11, P = .014), sCD14 (ρ = 0.12, P = .0046) as well as markers of inflammation and endothelial activation. Higher I-FABP levels were associated with lower systolic blood pressure (ρ = −0.14, P = .0015), delayed capillary refill time (ρ = 0.17, P = .00011), higher lactate level (ρ = 0.40, P < .0001), increasing stage of acute kidney injury (ρ = 0.20, P = .0034), and coma (P < .0001). Admission I-FABP levels ≥5.6 ng/mL were associated with a 7.4-fold higher relative risk of in-hospital death (95% confidence interval, 1.4–11, P = .0016). Conclusions Intestinal injury occurs commonly in children hospitalized with malaria and is associated with microbial translocation, systemic inflammation, tissue hypoperfusion, MODS, and fatal outcome.Keywords:
Organ dysfunction
The concept of and approach to multiple organ dysfunction syndrome (MODS), also known as progressive systems failure, multiple organ failure, and multiple system organ failure, have evolved over the last decade. Characterized by progressive but potentially reversible tissue damage and dysfunction of two or more organ systems that arise after a significant physiologic insult and its subsequent management, MODS evolves in the wake of a profound disruption of systemic homeostasis. Pre-existing illness, nutritional status, hospital course, and genetic variation all lead to the development of organ dysfunction in patients exposed to these risk factors. The ultimate outcome from MODS is influenced not only by a patient’s genetic and biological predisposition but also by specific management principles practiced by intensivists. This review details the clinical definitions, quantification, prevention, evaluation, support, and outcomes of organ dysfunction. A figure shows the increasing severity of organ dysfunction correlated with increasing intensive care unit mortality, and an algorithm details the approach to MODS. Tables list risk factors and prognosis for MODS, the multiple organ dysfunction (MOD) score, the sequential organ failure assessment (SOFA) score, intensive care unit interventions that reduce mortality or attenuate organ dysfunction along with unproven or disproven ICU interventions, and the temporal evolution of MODS. This review contains 1 figure, 7 tables, and 159 references.
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Multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in surgical intensive care units (SICUs). Multiple organ dysfunction syndrome remains the most important factor associated with mortality in the SICU. Illness severity scores such as the Acute Physiology and Chronic Health Evaluation-III (APACHE III) and the magnitude of the systemic inflammatory response syndrome (SIRS) at the time of SICU admission are useful in stratifying patients at risk for MODS and subsequent mortality. Assessment of key organ systems shows that mortality correlates with the overall severity of organ dysfunction and the number of involved organ systems, as well as to individual organs that fail. Despite the prognostic utility of SIRS/MODS, definitions of dysfunction of individual organs have shortcomings. The problem with quantitating MODS lies in the inability to adequately define organ dysfunction, especially of the gastrointestinal tract, liver, and central nervous system. Biological indicators of organ dysfunction may prove to be better markers for MODS in the future.
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Objective To investigate the value of gastric intramucosal pH(pHi) in the early prediction of critically ill patients with multiple organ dysfunction syndrome. Methods Twenty critically ill patients's gastric intramucosal pH immediately and 24 hours later were measured,then patients were divided into multiple organ dysfunction group(group A) and non multiple organ dysfunction group(group B) according to the diagnostic standard of multiple organ dysfunction syndrome.Group A was subdivided into 2 organ dysfunction group(A1) and more than 2 organ dysfunction group(A2).Gastric intramucosal pH of group A and group B were firstly,then A1 with A2 group. Results There were 9 cases with multiple organ dysfunction syndrome.Four cases with 2 organs dysfunction,5 cases with more than 2 organs dysfunction.Gastric intramucosal pH in group A wab lower than that in group B(P0.01),gastric intramucosal pH in group A2 was lower than that in group A1(P0.01). Conclusion The level of gastric intramucosal pH was revelant to multiple organ dysfunction syndrome.It is one of the important indicators in the early prediction of critically ill patients with multiple organ dysfunction syndrome.
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The concept of and approach to multiple organ dysfunction syndrome (MODS), also known as progressive systems failure, multiple organ failure, and multiple system organ failure, have evolved over the last decade. Characterized by progressive but potentially reversible tissue damage and dysfunction of two or more organ systems that arise after a significant physiologic insult and its subsequent management, MODS evolves in the wake of a profound disruption of systemic homeostasis. Pre-existing illness, nutritional status, hospital course, and genetic variation all lead to the development of organ dysfunction in patients exposed to these risk factors. The ultimate outcome from MODS is influenced not only by a patient’s genetic and biological predisposition but also by specific management principles practiced by intensivists. This review details the clinical definitions, quantification, prevention, evaluation, support, and outcomes of organ dysfunction. A figure shows the increasing severity of organ dysfunction correlated with increasing intensive care unit mortality, and an algorithm details the approach to MODS. Tables list risk factors and prognosis for MODS, the multiple organ dysfunction (MOD) score, the sequential organ failure assessment (SOFA) score, intensive care unit interventions that reduce mortality or attenuate organ dysfunction along with unproven or disproven ICU interventions, and the temporal evolution of MODS. This review contains 1 figure, 7 tables, and 159 references.
Organ dysfunction
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The concept of and approach to multiple organ dysfunction syndrome (MODS), also known as progressive systems failure, multiple organ failure, and multiple system organ failure, have evolved over the last decade. Characterized by progressive but potentially reversible tissue damage and dysfunction of two or more organ systems that arise after a significant physiologic insult and its subsequent management, MODS evolves in the wake of a profound disruption of systemic homeostasis. Pre-existing illness, nutritional status, hospital course, and genetic variation all lead to the development of organ dysfunction in patients exposed to these risk factors. The ultimate outcome from MODS is influenced not only by a patient’s genetic and biological predisposition but also by specific management principles practiced by intensivists. This review details the clinical definitions, quantification, prevention, evaluation, support, and outcomes of organ dysfunction. A figure shows the increasing severity of organ dysfunction correlated with increasing intensive care unit mortality, and an algorithm details the approach to MODS. Tables list risk factors and prognosis for MODS, the multiple organ dysfunction (MOD) score, the sequential organ failure assessment (SOFA) score, intensive care unit interventions that reduce mortality or attenuate organ dysfunction along with unproven or disproven ICU interventions, and the temporal evolution of MODS. This review contains 1 figure, 7 tables, and 159 references.
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There is as yet no precise definition of the multiple organ failure syndrome, or what is today more appropriately termed the multiple organ dysfunction syndrome (MODS). Clinically MODS can be considered as a sequential or concomitant occurrence of a significant derangement of function in two or more organ systems of the body, against a background of a critical illness. Organ dysfunction may be mild, moderate or severe, and multiple organs may show varying degrees of dysfunction. There is no universally acceptable classification system which defines parameters of organ specific failure. An ACCP/SCCM Consensus Conference which was held in 1991, defined MODS as “the presence of altered function in an acutely ill patient such that homeostasis cannot be maintained without intervention”. 1 This con
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Objective To detect the changes of interleukin-18 (IL-18) in plasma of trauma patients and evaluate their value in early warning of organ dysfunction. Methods A prospective study was carried out in 54 trauma patients admitted in from March 2001 to September 2002, which were divided into low injury severity score(ISS) group (Group L-ISS) and high ISS group (Group H-ISS). ELISA was applied to measure the level of IL-18 of blood samples that were collected on arrival, at days 4, 7 and 14 following admission. In the meantime, IL-18 level of plasma samples from patients with systemic inflammatory response syndrome (SIRS), sepsis and multiorgan dysfunction syndrome (MODS) was retrospectively analyzed so as to calculate the critical value of IL-18 in predicting organ dysfunction. Results After trauma, IL-18 concentration of plasma reached peak at days 4 and 7, and decreased gradually at day 14, which was significantly related to SIRS, sepsis and MODS, respectively. The IL-18 level was high relatively in plasma from patients with organ dysfunction. The higher IL-18 level in plasma within seven days after trauma indicated the severer organ dysfunction. Conclusion IL-18 is sensitive in early warning of organ dysfunction after trauma.
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Objectives: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Design: Secondary analysis of a prospective, cross-sectional, point prevalence study. Setting: International, multicenter PICUs. Patients: Pediatric patients with severe sepsis identified on five separate days over a 1-year period. Interventions: None. Measurements and Main Results: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis–associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) ( p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively ( p < 0.001). Conclusions: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.
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